Objective To investigate the effects of IL-6/JAK2/STAT3 on the biological behavior of oral squamous cancer cells.Methods The oral squamous cell carcinoma cell line was transfected with lentivirus, and the IL-6 gene was knocked down. Two control groups (no intervention group and blank vector group) were set up. The effect of IL-6 on the proliferation of oral squamous cell carcinoma cells was detected by CCK8 experiment and clonal formation experiment, the cellular cycle change was detected by flow cytometry, and the influences of IL-6 on invasion and migration ability of oral squamous cell carcinoma cells were detected by Transwell experiment. Then real-time fluorescence quantitative PCR and Western blot were used to detect the expressions of the downstream channel gene STAT3, JAK2, protein VEGFA related to tumor angiogenesis, cell cycle regulatory protein Cyclin B1, cell matrix deposition-related protein MMP2, apoptosis suppressor protein Survivin, and protein Snail and E-Cadherin related to epithelial-to-interstitial transformation in oral squamous cell carcinoma cells after downregulation of IL-6 gene expression.Results Compared with the control group, the oral squamous cell carcinoma cells with knockout IL-6 were significantly inhibited in proliferation rate, and the difference was statistically significant (P<0.05). The percentage of G1-phase cells in oral squamous cell carcinoma cells with knockout IL-6 decreased significantly while that of G2-phase cells increased significantly, and the differences were statistically significant (both P<0.05). The invasive ability and migration ability of oral squamous cell carcinoma cells with knockout IL-6 decreased significantly compared with the control cells, and the difference was statistically significant(P<0.05). Compared with the control group, the expressions of STAT3, JAK2, VEGFA, Cyclin B1, MMP2, Snail and Survivin protein decreased significantly while E-Cadherin protein expression increased apparently in oral squamous cell carcinoma cells with knockout IL-6 (all P<0.05).Conclusion IL-6/JAK2/STAT3 signaling pathway can promote proliferation and migration of oral squamous cell carcinoma.