One possible reason could be power. Maybe in the fanfic, there's a new source of power that Tsunade wants desperately and Naruto stands in her way to obtain it. So she betrays him to get to that power.
It could be due to a misunderstanding. For instance, Tsunade might be misled by false information about Naruto being involved in something bad for the village. In her haste to protect the village, she betrays Naruto without knowing the truth. She might later regret it when she discovers the real situation.
Another aspect could be related to her past or origin. If she has some hidden memories or a secret agenda tied to her existence as the Fem Kyubii, it could lead her to betray Naruto. For example, if there are some dark forces that are controlling or influencing her from her past, she may be forced to turn against Naruto against her will in a sense.
Perhaps in this fanfic, Tsunade kills Naruto out of desperation to save the village from a perceived greater threat. If there was a prophecy that Naruto's power would lead to the destruction of Konoha in a certain way, Tsunade, in her role as Hokage, might feel it her duty to stop him at all costs. This would be a very tragic turn as Naruto is seen as a hero in the original story.
One possible plot could be that Naruto discovers some dark secrets about Konoha's leadership. For example, he might find out that they were involved in unethical experiments in the past. This discovery could make him feel betrayed first, and then lead him to take actions that Konoha sees as betrayal, like refusing to follow orders or even teaming up with an enemy of Konoha who he believes has a more just cause.
One possibility could be a misunderstanding. Maybe Kakashi is framed for something that makes Naruto believe he has betrayed him. For example, an enemy could use a clone of Kakashi to perform a heinous act, and Naruto witnesses it without seeing the full picture.
One possible reason could be that Naruto discovers some dark secrets within Konoha. Maybe he finds out that the village elders have been using him all along, not truly caring about his well - being but only his power as a Jinchuriki. This realization could be so shocking that he decides to turn against the village.
The immediate effect would be a huge shock to Naruto. His trust in Tsunade would be shattered, and this could lead to a period of self - doubt for him. He might question his own judgment in trusting people.
One possible plot could be a training scenario. Naruto is blindfolded for a special training exercise, and Tsunade is overseeing it. Maybe Naruto has to rely on his other senses like hearing and smell to complete tasks while Tsunade observes and offers her tough - love guidance. It could also involve Naruto trying to prove himself to Tsunade in this unique situation.
Perhaps in the fanfic, Tsunade breaks Naruto's over - confidence. She might see him getting a bit too cocky and decides to put him in his place. She could do this through a series of tough training sessions or by making him face opponents that are stronger than he initially thought. This would be a way to humble Naruto and help him grow as a ninja.
One possible plot could be that Tsunade teaches Naruto advanced medical ninjutsu. Naruto, being a fast learner, quickly grasps the basic concepts but struggles with the more delicate aspects. Tsunade, with her tough - love teaching style, pushes Naruto to his limits until he finally masters it and is able to use medical ninjutsu in combat to heal his comrades.
One possibility is that there's a mission where Naruto and Tsunade are paired together. Along the way, Naruto gets into some mischief and tries to tickle Tsunade to cheer her up when she's feeling stressed about the mission. Tsunade initially acts annoyed but then realizes it's all in good fun. This could also be a way for Naruto to bond more with Tsunade on a personal level, rather than just as the Hokage and a ninja.