In this study, we revealed the growth‐promoting role of RPAP2 in HCC cells with the following lines of evidence: 1) RPAP2 is upregulated in human HCC tissues, which is associated with a poor prognosis for patients; 2) RPAP2 knockdown inhibits the growth and survival of HCC cells, accompanied by a reduction in mTOR activity and induction of G1 phase arrest; and 3) RPAP2 depletion significantly suppresses tumor growth, whereas RPAP2 overexpression promotes tumor growth in the xenograft model (Figure 1; Figures S1,S2, Supporting Information). This evidence concerns the gene RPAP2 and hepatocellular carcinoma.