To explore the molecular mechanism by which ginsenoside Rh2 (G-Rh2) inhibits prostate cancer by regulating vascular growth. Different concentrations of G-Rh2 with three prostate cancer cell lines (LNCaP, PC3 and DU145) were transplanted in nude mice, and tumor mass volume was measured over time. LNCaP, PC3 and DU145 were co-cultured with vascular endothelial cells to determine the optimal concentration of G-Rh2 by MTT assay. LNCaP, PC3 and DU145 were cultured under the selected concentration (0, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL) of G-Rh2, and the expression levels of CD31, VEGF, PDGF and CNNM1 detected by qRT-PCR and western blot. The expression pattern of CD31 was detected in CNNM1 overexpressed and knockout LNCaP, PC3 and DU145 cells under G-Rh2. G-Rh2 significantly inhibited the growth of all three prostate cancer cell lines in the dorsum of nude mice (P <0.05), and the increment rate of vascular endothelial cells co-cultured with LNCaP, PC3 and DU145 (P <0.05). The expression of CD31, VEGF, PDGF and CNNM1 genes in LNCaP, PC3 and DU145 cells was inhibited by G-Rh2. Overexpression of CNNM1 reversed the inhibitory effect of G-Rh2 on the expression of CD31 in these cells (P <0.05), while the function of knockout of CNNM1 and the inhibitory effect of G-Rh2 appeared to be similar (P <0.05). In conclusion, G-Rh2 inhibited prostate cancer growth by inhibiting its angiogenesis through decreasing the expression of CNNM1 in the cancer cells.