Objective：To analyze the effect and mechanism of verbascoside on the migration and invasion of oral squamous cell carcinoma. Methods：The expression profiles of HN4 protein in oral squamous cell carcinoma cells treated with verbascoside and the blank control group were analyzed by mass spectrometry. Proteins with high abundance and significantly increased expression after verbascoside treatment were screened. The results of mass spectrometry were verified by Western blotting. The expression of key proteins in HN4 cells was interfered by shRNA to analyze verbascoside. Effects of verbascoside on migration and invasion of squamous cell carcinoma HN4 cells were analyzed. Results：The results of mass spectrometry analysis showed that 18 proteins，including Max，MPRSS11F，ROBO4，AP4E1，and etc，was significantly increased in oral squamous cell carcinoma HN4 cells after treatment with verbascoside（fold change>1.5）. The Max proteins with the most obvious changes were detected by Western blotting. The results of Western blotting were consistent with those of mass spectrometry microarray. shRNA interfered with the expression of Max in oral squamous cell carcinoma HN4 cells. qRT-PCR and Western blotting showed that the expression of Max in HN4 cells was significantly down-regulated. Further stimulation of HN4 cells with verbascoside showed that the migration and invasion of HN4 cells were significantly inhibited. However，the ability of verbascoside to inhibit the migration and invasion of HN4 cells decreased significantly after knockdown of Max protein. Conclusion：It is possible that verbascoside inhibits the migration and invasion of oral squamous cell carcinoma cells by enhancing the expression of Max in oral squamous cell carcinoma cells.