The purpose of this study was to explore the effects of MMP-2 silencing on the invasion and growth of laryngeal squamous cell carcinoma (LSCC). Hep-2 cells were transfected with MMP-2-RNAi-Lentivirus, and MMP-2 expression and invasive properties of the cells were evaluated. The experimental tumors in the nude mice were intratumorally injected with the same recombinant lentivirus. The inhibition of tumor growth was observed. The expression of MMP-2 protein in MMP-2 siRNA transfected Hep-2 cells was effectively suppressed. Both the viability and invasive ability of Hep-2 cells were significantly inhibited. The average weight and volume of tumor in MMP-2-RNAi-Lentivirus treated group were significantly lower than those in the control group (P < 0.01). The PCNA index was obviously lower in MMP-2 RNAi treated tumors (P < 0.01). In conclusion, MMP-2 silencing by recombinant lentivirus mediated RNA interference can inhibit invasion and growth of LSCC, and MMP-2 might be a potential target for gene therapy in LSCC.