Purpose of investigation: The present study aimed to investigate the effect of Piwil2 on proliferation and invasion of cervical cancer cells. Materials and Methods: Thirty-two HPV-positive or negative cervical cancer tissues and corresponding normal adjacent cervical tissues were obtained from General Hospital of Lanzhou Military Region. Piwil2 expression in these tissue samples, as well as two cervical cell lines were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical. A specific short hairpin RNA (shRNA) was used to knockdown the Piwil2 gene in SiHa cells. CCK-8 assay and flow cytometry (FCM) was used to evaluate cell proliferation. Cell invasion was detected by transwell chambers assays. Immunoblotting was used to assess the effect on relevant proteins. Result: In the early stage (I A1 – I B1) of curvival, 84.4% (27/32) tumor tissues have a more predominant expression of Piwil2 than the normal adjacent samples. Piwil2 overexpression was correlated with HPV16 infection (p < 0.05). Knockdown of Piwil2 gene in SiHa cells inhibited cell growth and invasion, and downregulated matrix metalloproteinase- 9 (MMP-9) compared to scrambled shRNA transfected cells. Further analysis revealed that downregulation of Piwil2 gene induced inhibition of the MAPK signaling pathway activity. Conclusion: Piwil2, which stimulated by HPV16 infection, plays an important role in regulating proliferation and invasion of cervical cells by regulating MMP-9 expression via alternation of the MAPK signaling pathway.