〔Abstract〕 Objective To explore the biological effects of Nav1.6-RNAi on the proliferation of oral squamous cell carcinoma cell lines and analyze its possible regulatory mechanism. Methods Immunohistochemistry, Western blot and qRT-PCR were used to detect the expression of Nav1.6 in oral squamous cell carcinoma tissues. After Nav1.6-RNAi transfected into oral squamous cell carcinoma, Western blot was used to validate the expression of CyclinD1, C-myc, AKT and p-AKT. Cell cycle was also detected by flow cytometry. Results Immunohistochemistry, Western blot and qRT-PCR showed that the expression of Nav1.6 in oral squamous cell carcinoma tissues was significantly higher than that in normal oral tissues(P<0.05). After Nav1.6-RNAi transfected into oral squamous cell carcinoma, the expression of CyclinD1, C-myc and p-AKT protein significantly decreased compared with the control group(P<0.05), and the cells in S phase significantly reduced. Conclusion Voltage-gated sodium channel Nav1.6 can affect the proliferation of oral squamous cell carcinoma through the AKT pathway.