Objective  To investigate the relationship between the expression of phosphatidylinositol-5 (GPC5) and the genesis and prognosis of prostate cancer.Methods  From February 2013 to May 2015, 104 cases of prostate cancer in our hospital as the observation group were selected. And 89 cases of benign prostatic hyperplasia were selected as the control group. The expression of GPC5 protein was detected by immunohistochemical staining and the expression of GPC5 mRNA was detected by fluorescent quantitative PCR. Highly invasiveprostate cancer PC3 cell lines, low invasive prostate cancer LNCaP cell lines and normal prostate epithelial cell line RWPE-1 cells were selected. The expression of GPC5 protein was detected by Western blot. Results  The relative expression of GPC5 mRNA and the GPC5 protein positive expression rate in the observation group were (0.64±0.15) and 34.62%, significantly lower than that of the control group (P<0.05). Preoperative PSA ≥4 ng/mL, tumor staging T3, Gleason score ≥8 in patients with GPC5 protein positive expression rates were 20.34%, 19.44% and 21.05%, significantly lower than the preoperative PSA<4 ng/mL staging, tumor staging T2 and Gleason score <8 patients (P<0.05). The median overall survival time of GPC5 positive patients was 39.04 months, significantly longer than that in patients with negative GPC5 protein expression (P<0.05). The expression of GPC5 protein in PC3 cells was (0.083±0.024), significantly lower than that in LNcaP and RWPE-1 cells (P<0.05). The expression of GPC5 protein in LNcaP cells was (0.301±0.083), significantly lower than that in RWPE-1 cells (P<0.05).Conclusions  The expression of GPC5 mRNA and protein in prostate cancer is down regulated, which is related to clinicopathological features and prognosis, it is worthy of further study.