Objective:To certify that KSHV could infect prostate non-tumorigenic cells RWPE-1 and prostate cancer cells PC-3 effectively,and to investigate the alteration of the Wnt signalling pathway post-infection. Methods:Harvested from primary effusion lymphoma (PEL) cells BC-3,the KSHV virion- supernatant was used to infect RWPE-1 and PC-3 cells. The cytopathic effect (CPE) of prostate cells was observed post-infection and the replication of KSHV in prostate cells was detected by RT-PCR and Western blot. The expression of β-catenin in both cytoplasm and nuclei was detected by Western blot. Results:Post-infection,CPE was appeared in RWPE-1 but not in PC-3. KSHV ORF50 mRNA was detected in PC-3 cells by RT-PCR. And the specific band of vIL-6 appeared as expected in Western blot detection in both RWPE-1 and PC-3 cells extract. The expression of β-catenin in both cytoplasm and nuclei of RWPE-1 were up-regulated post-infection. Conclusion:KSHV could infect prostate non- tumorigenic cells RWPE-1 and prostate cancer cells PC-3 effectively and trigger the Wnt signaling pathway in RWPE-1 post-infection.