Gastric cancer is a prevalent cancer and chemotherapy is a main treatment for patients. Docetaxel is commonly used as a chemotherapeutic drug for gastric cancer patients. With the increasing emergence of docetaxel resistance, exploring the mechanism of chemoresistance may improve prognosis of patients. In this study, we found that overexpressed miR-361-5p suppressed chemoresistance to docetaxel of gastric cancer cells (SGC-7901, MKN-28) by decreasing IC50 values of docetaxel while increasing cell apoptosis rate, especially in docetaxel resistant SGC-7901 cells. Further researches revealed that overexpressed miR-361-5p inhibited chemoresistance through inhibiting autophagy with a characteristic of declined number of LC3+ puncta, decreased expression of Beclin-1 and the ratio of LC3 II/I and increased expression of p62. Bioinformatics study and Luciferase reporter assay indicated that FOXM1 was a target of miR-361-5p and FOXM1 was negatively regulated by miR-361-5p in gastric cancer. Simultaneously, overexpression of FOXM1 counteracted the inhibitory effects of miR-361-5p on chemoresistance of gastric cancer cells through activating autophagy, further certifying the targeting relationship between the two. Moreover, overexpressed miR-361-5p activated the PI3K/Akt/mTOR pathway. The adding of PI3K inhibitor LY294002 played an opposite role to miR-361-5p mimic by inducing autophagy and chemoresistance to docetaxel of gastric cancer cells compared with docetaxel + miR-361-5p mimic group, indicating that miR-361-5p suppressed autophagy-induced chemoresistance via the PI3K/Akt/mTOR pathway in gastric cancer cells. In conclusion, we found that miR-361-5p suppressed autophagy-induced chemoresistance of gastric cancer cells through targeting FOXM1 via the PI3K/Akt/mTOR pathway, providing a foundation for the mechanism research and treatment of gastric cancer.

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