Abstract: The aim of this study was to investigate the effect of dihydroartemisinin（DHA） on prostate cancer PC-3 cells xenograft model. Prostate cancer PC-3 cells were transplanted to establish the classic xenograft mode. After tumor formation, we researched on it with DHA intervention once every two days. On the 13 th day, samples were collected to calculate the rate of tumor inhibition. The morphological changes were observed by light microscopy and electron microscopy. The apoptotic cells were counted and the apoptotic rate was calculated by TUNEL; the expression of uhrf1, dnmt1 and p16^{ink4 a} mRNA were detected by quantitative real-time PCR; the expression at protein levels of UHRF1, DNMT1 and P16^{ink4 a} were observed by Western Blot; the cellular location and expression of UHRF1, DNMT1 and P16^{ink4 a}protein were detected by immunohistochemical methods. Our data showed that DHA could inhibit the growth of PC-3 cells in nude mice, induce apoptosis and necrotic morphological changes. RT-qPCR, Western Blot and immunohistochemistry showed that DHA could decrease the expression levels of uhrf1 and dnmt1 in PC-3 cells and increase the expression level of p16^{ink4 a}. In summary, DHA could effectively inhibit the growth of prostate cancer xenograft in nude mice. The mechanism may be related to the induction of apoptosis of PC-3 cells by down-regulating the expression of uhrf1, dnmt1 and restoring the expression of tumor suppressor gene p16^{ink4 a}.