Abstract: Objective：To investigate the effect of lentinan on the proliferation of oral squamous cell carcinoma cell HN4 and its mechanism. Methods：In vitro MTT assay was used to detect the growth inhibition of HN4 cells. The effect of lentinan on the apoptosis of HN4 cells was detected by AO/EB method. The expression of Bcl-2 and Bax in HN4 tumor cells was detected by Western blot . Results：Lentinan could significantly inhibit the growth and proliferation of oral squamous cell carcinoma HN4 cells. AO/EB staining showed that after lentinan stimulated the cells, apoptosis of HN4 cells was observed under a fluorescence microscope, staining increased, nuclear pyknosis and orange-red staining were observed. Western blot results showed that lentinan could decrease the expression of Bcl-2, increase the expression of Bax and increase the ratio of Bax/Bcl-2 in HN4 cells. Conclusions：Lentinan could inhibit the proliferation of oral squamous cell carcinoma HN4 cells in vitro and induce the apoptosis of HN4 cells.