Abstract: Objective To analyze the mechanism of AnnexinA2 abnormal expression in invasion and metastasis of prostate cancer(PC). Methods A total of 85 PC specimens were paraffin-embedded and confirmed pathologically. AnnexinA2 expression in these specimens was determined by immunohistochemical staining. Western blot assay was conducted to detect AnnexinA2 expression in LNCaP and PC-3 with low metastasis potency, as well as and C4-2B and PC-3M with high metastasis potency. After siRNA was successfully performed in PC-3 cells to down-regulate AnnexinA2 expression, cell proliferation assay was performed by MTT method. Expression of MMP-2 and MMP-9 were detected by Western blot. Invasive abilities of PC-3 were detected by Transwell cabinet test in vitro. Migration abilities of PC-3 cells were detected by scratch test. Results The positive rates of AnnexinA2 expression were 77.5%(31/40), 58.3%(21/36), 11.1%(1/9) in the cases of Gleason scores 5~6, 7 and 8~10 in PC, respectively, with significant difference (P< 0.05). AnnexinA2 expression in C4-2B and PC-3M groups with high metastasis potency were lower than those in LNCaP and PC-3 groups with low metastasis potency (P<0.05). After siRNA was successfully performed in PC-3 cells to down-regulate AnnexinA2 expression, the growth speed in PC-3-ANXA2-siRNA cells was faster than those in PC-3, PC-3-Lip and PC-3-empty vector cells (P<0.05). AnnexinA2 expression in PC-3-ANXA2-siRNA cells was decreased while the expression of MMP-2 and MMP-9 were increased. Invasive ability of PC-3-ANXA2-siRNA cells detected by Transwell cabinet test was increased in vitro, and migrate abilities of PC-3-ANXA2-siRNA cells detected by scratch test was increased in vitro. Conclusion Down-regulating AnnexinA2 expression could promote invasion and metastasis of PC by up-regulating MMP-2 and MMP-9 expression.