Objective: To investigate the effect of interleukin 6/Janus kinase 2/signal transducer and activator of transcription 3 (IL-6/JAK2/STAT3) on the biological behavior of oral squamous cell carcinoma (OSCC). Methods: OSCC cells were transfected with the designed lentiviral vector plasmid pGMLV-SB3 (experimental group) and the corresponding negative control plasmid pGMLV-SB3-shNC (control group); 48 hours after transfection, a liposome transfection kit (Sigma, USA) was used for lentivirus packaging; after virus packaging, a medium containing pGMLV-SB3 lentiviral vector was added and cultured for 24 h; the cells were harvested, and RNA was extracted; Transwell chamber assay (Sigma, USA) was used to detect cell migration and invasion ability; dot-enzyme-linked immunosorbent assay (ELISA) kit was used to detect the level of interleukin 6 (IL-6) in the culture supernatant, while serum IL-6 level was measured by ELISA. Results: The expressions of IL-6, JAK2, and STAT3 in the experimental group were significantly raised, as compared to the control group (P < 0.05); the apoptosis rate of OSCC cells in the experimental group, which was detected by flow cytometry 48 h after transfection, was significantly higher than that of cells in the control group (P < 0.05); and there was a significant improvement in the experimental group’s cell migration and invasion ability, as compared to that of the control group (P < 0.05). Conclusion: The IL-6/JAK2/STAT3 signaling pathway plays an important role in the migration and invasion of OSCC cells. Inhibiting the expression of IL-6 can inhibit the growth and proliferation of OSCC cells as well as reduce their ability to invade and migrate. These results provide a new target for the treatment of OSCC.