Objective：To investigate the effects of hepatocyte cell adhesion molecule（hepaCAM） overexpression adenovirus combined with crocin on cell proliferation in prostate cancer cell line DU145. Methods：MTT assay was used to evaluate the effect of cell pro－liferation. Colony formation test was used to measure colony formation rate of single cell. Real-time quantitative PCR（qPCR） assay and Western blot were used to detect mRNA and protein expression of cyclinD1 and PCNA respectively. Results：After being treated with hepaCAM overexpression adenovirus or crocin alone，the proliferation of DU145 cell was inhibited[IR=（12.0±2.0）%，（22.0±1.0）%]，but the effect was more remarkable when the cells being treated with hepaCAM overexpression adenovirus and crocin combined[IR=（54.0±1.0）%，P=0.000]. Expression of cyclinD1 mRNA was down-regulated after being treated with hepaCAM over－expression adenovirus and crocin combined compared with being treated with crocin alone detected by qPCR（P=0.048），and prolif－erating cell nuclear antigen（PCNA） mRNA was down-regulated after being treated with hepaCAM overexpression adenovirus and crocin combined compared with being treated with hepaCAM overexpression adenovirus or crocin alone（P=0.047，P=0.006）. Western blot showed that compared with hepaCAM group or crocin group，expressin of cyclinD1 protein was down-regulated in hepaCAM and crocin combined group（P=0.002，P=0.002），meanwhile expression of PCNA protein was also down-regulated（P=0.000，P=0.003）. Conclusion：hepaCAM overexpression adenovirus combined with crocin can inhibit cell proliferation of prostate cancer cell line DU145 and the machanism is associated with down-regulation of cyclinD1 and PCNA expression.