Inositol polyphosphate 4‐phosphatase B (INPP4B) has been identified as a tumour suppressor in different human cancers. However, the role of INPP4B in the angiogenesis of human prostate cancer cells remains unclear. In this study, we first compared the expression of INPP4B between prostate cancer tissues and tumour‐adjacent normal prostate tissues using immunohistochemistry. Then, we explored the role of INPP4B in prostate cancer progression via transfection of a Flag‐INPP4B plasmid into PC3 and DU145 cells in vitro and in vivo. Our results showed that reduced INPP4B staining was significantly correlated with the tumour‐node‐metastasis stage. Moreover, transfection with Flag‐INPP4B plasmid suppressed the migration and invasion of prostate cancer cells through inactivating the PI3K/Akt signalling pathway, at the same time decreased vascular endothelial growth factor secretion and suppressed human umbilical vein endothelial cells proliferation and tube formation. Futhermore, it was also found that INPP4B could inhibit tumour growth and angiogenesis in vivo. Altogether, our results supported that INPP4B acted as a tumour suppressor in human prostate cancer, and provided insights into development of a targeted therapy for this disease.