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.