The cell division cycle-associated 7-like protein (CDCA7L) is a recently-identified target gene of c-Myc which can also interact with c-Myc. It is known to be upregulated in many tumors, however, its role in tumor progression remains unclear. We investigated the role of CDCA7L expression in hepatocellular carcinoma (HCC). We confirmed that CDCA7L is strongly upregulated in human HCC, and demonstrated that ectopic overexpression of CDCA7L promotes HCC cell proliferation and colony formation. Conversely, knockdown of CDCA7L inhibits these malignant phenotypes. In an in vivo model, subcutaneous transplantation of the tumor in nude mice showed that overexpression of CDCA7L can accelerate the tumor growth rate. Mechanistic analyses indicated that CDCA7L was able to activate the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway and regulate the cell cycle, thus promoting HCC progression. Collectively, these findings show that CDCA7L plays a role in promoting the development of HCC and may constitute a potential therapeutic target in HCC.