Objective:To study the effects of phosphatase of regenerating liver cell-1(PRL-1) small interfering RNA(siRNA)on inva-sion of tongue cancer cells(TCA8113) and the mechanism. Methods:After tongue squamous cancer cell line TCA8113 being trans-fected by PRL-1 siRNA,the mRNA and protein of PRL-1 and matrix metalloproteinase-2(MMP-2) and matrix metalloproteinase-9 (MMP-9) were determined by real-time PCR and Western blot assay,respectively. TCA8113 cell invasiveness was detected through Transwell chamber using model test. Results:After transfection by PRL-1 siRNA,the level of mRNA(0.425 0±0.010 0) and pro-tein(2.720 0±0.110 0) of PRL-1 was down-regulated(P=0.000,P=0.000). The mRNA level of MMP-2 and MMP-9(0.562 2±0.180 0,0.617 1±0.100 0)as well as the protein level of MMP-2 and MMP-9(0.592 4±0.010 0,0.476 2±0.020 0) were decreased obviously(P=0.024,P=0.010,P=0.000,P=0.000). The invasion ability of human tongue squamous cancer cell was reduced(64.33±4.04)(P=0.000). Conclusion:PRL-1 gene might play an important role in development of human oral squamous cell carcinoma and down-regulation of PRL-1 could inhibit invasion of human tongue squamous cancer cell. This may be related to the lower expression of MMP-2 and MMP-9.