PRIM1 plays an important role during oncogenesis, however it has never been reported in liver cancer, and thus our objective is to explore the role of PRIM1 in liver cancer. We selected RNAseq data of 50 paired liver cancer samples from the Cancer Gene Atlas (TCGA), and then bioinformatics methods and Mann-Whitney U test were used to analyze the correlation between PRIM1 and the clinical pathological stage of liver cancer. Quantitative polymerase chain reaction (QPCR) was used to detect mRNA expression of PRIM1 in BEL-7404, BCL-7402, HepG2 and SMMC-7721 cell lines. LV-PRIM1-RNAi was transfected into BEL-7404 and SMMC-7721 cells by lentivirus, and then Celigo imaging cytometer, Caspase3/7 Assay, flow cytometry and MTT assay were used to detect the proliferation and apoptosis of BEL-7404 and SMMC-7721 cells with ≥50% gene reduction rate after lentivirus transfection detected by QPCR. BEL-7404 and SMMC-7721 carrying PRIM1 gene were used for oncogenesis in vitro to observe the weight and fluorescence intensity of the tumor. Bioinformatics method was used to obtain the information about PRIM1 gene, and the correlation between PRIM1 and clinical pathological stage of liver cancer was analyzed by Mann-Whitney U test. QPCR results showed that PRIM1 was expressed in BEL-7404, BCL-7402, HepG2 and SMMC-7721 cell lines, which was highest in BCL-7404 cell line. Celigo imaging cytometer, Caspase3/7 Assay, flow cytometry and MTT assay showed that the proliferative ability of BEL-7404 and SMMC-7721 were decreased after LV-PRIM1-RNAi transfection. Furthermore, the weight and the fluorescence intensity of the tumors in vitro formed by LV-PRIM1-RNAi cells on SCID mice were decreased. So, interference of PRIM1 expression can inhibit the proliferation of BEL-7404 and SMMC-7721 cells, as well as induce the apoptosis of liver cancer cells.