The expression of POLDIP3-β (POLDIP3 transcript lacking exon 3 and 29 amino acids) was significantly upregulated in liver cancer tissues compared with paired adjacent normal liver tissues. The functional experiments in vitro and in vivo have showed that POLDIP3-β overexpression significantly increased the proliferation and migration of HCC cells and promoted the growth of xenotransplantation. The above results have indicated that POLDIP3-β will be a potential target for the treatment of liver cancer. This evidence concerns the gene POLDIP3 and liver cancer.