To investigate the effect of Bin1 gene on Tau phosphorylation and the p38MAPK/NF-κB pathway in the Alzheimer’s disease (AD) cell model. Methods: (1) The Bin1 overexpression plasmid and Bin1 siRNA were constructed respectively. The expression of Bin1 was detected by qPCR, and the fragment with the best effect was selected to transfect PC12 cells. (2) The transfected PC12 cells were induced by Aβ25-35 to establish the AD cell model. The mRNA expression of Tau and p-Tau was detected by qPCR to verify the successful construction of the AD model cells. The viability of model cells was detected by MTT and caspase-3. (3) The experiment included 4 groups: blank group, AD model group, overexpression group, and siRNA group. (4) Western blot was used to detect the expression level of Bin1 and the protein levels of Tau, phosphorylated Tau (p-tau, ser396 site), p38MAPK, and NF-κB in each group. (5) The level of NO in the cell supernatant was detected by a biochemical kit. Inflammatory factors such as TNFα and IL-1β in the cell supernatant were detected by ELISA. Re? sults: (1) Bin1 overexpression plasmid significantly up-regulated Bin1 protein expression (P<0.01), and siRNA significantly down-regulated Bin1 protein expression (P<0.01). (2) MTT assay showed that cell survival in the AD model group was significantly lower than that in the blank group (P<0.01). Detection of caspase-3 activity showed that it was significantly higher in the AD model group than that in the blank group (P<0.01). (3) Western blot revealed that Bin1 expression was significantly greater in the AD model group and overexpression group than that in the blank group (P<0.01) and significantly lower in the siRNA group than that in the blank group (P<0.01). The protein expression of Tau and p-Tau (Ser396) in the blank group, siRNA group, AD model group, and overexpression group increased in the order listed, and pairwise comparison showed that the difference was statistically significant (P<0.05). (4) Compared with that in the AD model group, the expression of p38MAPK and NF-κB in the overexpression group increased significantly (P<0.05); the expression of p38MAPK and NF-κB in the siRNA group was decreased significantly (P<0.05). (5) The expression levels of IL-1 β, TNF-α, and NO in the blank group, siRNA group, AD model group, and overexpression group were increased in that order, and the differences were statistically significant (P<0.01). Conclusion: Bin1 may affect the signaling pathway of p38MAPK/NF-κB and be involved in the abnormal phosphorylation of tau protein, which leads to the sustained progression of AD.