Abstract: Objective：To study the effects of dihydromyricetin (DHM) on cell proliferation and apoptosis of head and neck squamous cell carcinoma (HNSCC). Methods：SCC-25 cancer cells were treated with 12.5, 25, 50 μmol/L DHM for 6, 12, and 24 h. SCC-25 cell apoptosis was detected by flow cytometry. Immunofluorescence was used to observe the emergence of autophagosomes in HNSCC cells. Western blotting was used to detect the expression of apoptosis and autophagy markers in SCC-25. Results：After treatment of 12.5, 25, and 50 μmol/L DHM for 24 h, the apoptosis of SCC-25 cells gradually increased; the apoptotic markers CL-PARP, Bax, and CL-casp3 gradually increased and Bcl-2 gradually decreased (P＜0.05). After treatment of 12.5, 25, and 50 μmol/L DHM for 24 h, in line with the apoptosis, the autophagy markers of SCC-25 cells gradually changed, the p-STAT3 expression was up-regulated; the ratio of LC3 Ⅱ /LC3 Ⅰ gradually increased, Beclin 1 increased, p62 gradually decreased (P＜0.05). Inhibition of autophagy could promote apoptosis of SCC-25 cells which were induced by DHM, increase apoptosis markers CL-PARP and Bax, and decrease Bcl-2 (P＜0.05). Conclusions：DHM can induce apoptosis and increase autophagy of HNSCC cells. The mechanism is related to STAT3 signaling pathway. Inhibition of autophagy can promote apoptosis of HNSCC cells induced by DHM.