Going by the facts offered by the last chapter, it can be argued that Goku has fought against opponents with equal or more strength than Saitama's in Dragon Ball's history. So a single Serious Punch from the bald hero would not be enough to destroy him as of yet.
The mere comparison of strength between the two characters is crazy. Goku is an extraterrestrial being who has to lose a fight in order to get stronger. Saitama is a man that can defeat any foe with a single punch. If the two of them were to face off in a one-on-one battle, Saitama would easily win.
Boros. Boros was the first on-screen opponent of Saitama that survived after getting punched, much to his surprise. In his fight with Saitama, Boros was hit with 3 normal punches, a Consecutive Normal Punches attack, as well as the shockwave from the hero's Serious Punch.
Immense Durability: Boros was shown to be amazingly resilient, to the point of being the first opponent of Saitama to survive after being hit directly by his normal punch, despite having his full power sealed by his armor.
This matchup is too close to decide with absolute certainty, but, in all likelihood, Saitama would claim victory. The fight would ultimately come down to who can last the longest, and Saitama is physically unmatched in every regard. A single punch would floor Goku, but the Zenkai Boost may not be enough to help.
Thus, it is safe to say that Limit-breaker Saitama cannot beat Goku in his Ultra Instinct form. It is far too powerful a transformation to contend with. Even if Bald Cape lands his Zero Punch, Goku has been seen multiple times being more than capable of taking a hit.
At one point, the protagonist of One Punch Man even slapped himself. While he gave himself a huge red mark, he seemed mostly unaffected by it, which suggests that he could likely withstand his own punch as well.
One Punch Man is a gag manga series, and the Caped Baldy was hurt in the most bizarre manner. A cat had scratched Saitama, and he screamed in pain. Technically, he was hurt by a cat, and the community jokes about how Boros couldn't do much compared to something as harmless as a cat.
It would be tough for Saitama to punch Beerus, seeing how this God was able to easily evade all of Goku's attacks even in his Super Saiyan form. Even when Goku becomes a Super Saiyan God, Beerus is able to defeat him after a mighty battle.
Immeasurable Strength: Saitama possesses an immeasurable amount strength and as a result is capable of destroying powerful monsters and villains with a single one punch (though this strength is not limited to punches).
Saitama could defeat Deadpool with one punch, but then Deadpool would heal and come back to life.
Goku wins this. Sure, Goku risky fighting style may lead Saitama to outpace him from time to time - but Goku has just that much raw power that Saitama simply lacks. Not to mention, we know he's smart enough to use his highest Kaiohken in a last burst, since it's exactly what he did against Frieza.
If Saitama trained the same way Goku did he would become the absolute most powerful being in fiction far above anyone in dragonball possibly even Zeno and that is no exaggeration. He would literally “one punch” everyone.
Unfortunately, since Saitama cannot also elevate his strength into another form, it would be unfair to compare Super Saiyan Goku to base Saitama. In terms of base form strength, Saitama from One Punch man takes home the win against Goku.
It is true that we have not seen Saitama's full power, and his fight with the God of his universe is fast approaching, but until we see him at his full potential, it is clear that Saitama is no match for Zeno now.
Saitama might be powerful, but even his physical strength cannot match Goku's strength. It should also be noted how Goku's Ultra instinct essentially scared the gods of destruction. Whether they're in the One Punch Man or Dragon Ball universe, Goku would easily be able to kill Saitama without much effort.
Saitama has never been shown to be sick or even affected by sickness.
Shonen Jump heroes are generally known for their ridiculous strength; however, One-Punch Man's Saitama is on a completely different level. Renowned for being able to end almost any fight in one punch, he just might be able to defeat Naruto — or any other shonen protagonist — in a one-on-one fight.
Saitama, being someone who is capable of shaping the entire world, feels pain when he lands awkwardly. Similarly, he also expressed his pain when a cat scratched his face. A cat's scratch is infinitesimally less powerful in comparison to an attack launched by the likes of Boros and Garou.
After Garou killed Genos in front of his eyes, Saitama felt pain and suffering for the very first time since he obtained his amazing strength. He realized that he could not call himself a hero if he let his friends die, and these violent emotions made him even more powerful than before.
He exhibits the same strength effortlessly and yet still has more room for growth. At this point, he hasn't ever needed to use his full power, whereas Goku frequently needs to reach his limits. All in all, Saitama wins this competition.
Saitama can not “one-punch” Goku. Goku has the durability to withstand universe busting attacks, in his significantly weaker forms.