Though there are several candidates for the strongest ninja in the world of Naruto, it's undeniable that the First Hokage, Hashirama Senju, is a top contender. Despite his strength, however, he died at a young age, with no explanation given in the series. It's likely that he died in the First Shinobi World War, which leaves a question: who could have killed someone labeled "the Shinobi God?"
Hashirama was the heir of the Senju, one of the most powerful clans during the Warring States Period, when the constant conflict between countries forced even the children of the mercenary shinobi clans to go to war. At a young age, Hashirama met a member of the most powerful rival clan, Madara Uchiha, and the two started dreaming of a way to end the conflict. They founded Konohagakure, the first of the shinobi Hidden Villages, and unified the Senju, Uchiha, and their affiliated clans, starting a brief era of peaceful coexistence. Hashirama became the First Hokage, but Madara grew disillusioned with their dream and started attacking Konoha. The two were regarded as the most powerful shinobi in history, and yet Senju always bested Madara with ease, even when the latter subdued Kurama, the Nine-Tailed Fox.
Senju's powerful abilities come from his heritage as a descendant of Asura Otsutsuki, the younger son of Haguromo, aka the Sage of the Six Paths, the god and ancestor of all shinobi and the son of the alien goddess Kaguya. The Senju inherited Asura's powerful life force and chakra, which Hashirama eventually manifested his unique Wood Release Jutsu. The Wood Release Jutsu allowed Hashirama to subdue and control the dangerous Tailed Beasts, which let him capture and distribute them among the Hidden Villages in an attempt to maintain peace. Hashirama was proficient in all five basic nature transformations, along with Yin and Yang Release. Thanks to his large chakra reserves, he could use senjutsu and Sage Mode with ease. He also possessed unmatched regenerative abilities that allowed him to heal any wounds, to the point that his DNA was highly coveted and used later to create clones.
With such an impressive array of powers, the mystery of Hashirama's death becomes even more compelling. The only thing stated in the series is that he died in battle during or shortly before the First Shinobi World War. Fans have many theories about his departure, with the most compelling being one that relates Hashirama's death to the overuse of his abilities. Hashirama's regeneration was based on cell division, as is the case with the Creation Rebirth jutsu inherited by his niece, Tsunade. However, Creation Rebirth is a forbidden technique because it reduces the lifespan of a person by increasing cellular activity. Since Hashirama had a similar ability, one that was potentially active all the time, it is plausible that it reduced his life drastically, more so in conjunction with his Wood Release which, to create new life, consumes a huge amount of chakra from the user.
The statement that Hashirama died in battle could be an inconsistency then, because if Madara was unable to kill him, it stands to reason nobody else could. In fact, when Hashirama's corpse is reanimated by Orochimaru, it appears without injuries - notable since the technique gives the reanimated body the same appearance that the person had at the time of their death. Another possible explanation is that Hashirama was actually previously injured during his final battle with Madara at the Valley of the End but he hid the extent of the damage from everyone else. Sometime later, his injuries overwhelmed his regenerative abilities, perhaps weakening him enough that an undisclosed enemy could finish him off.
The mystery surrounding Hashirama's death only serves to add even more mystique to his role as the Shinobi God. It is very likely that the death of Hashirama Senju will remain one of Naruto's biggest mysteries for good, unless the sequel Boruto addresses it at some point.