Objective To study the expression and roles of midkine (MDK) in human hepatocellular carcinoma (HCC). Methods A total of 50 HCC tissues and tumor adjacent tissues were collected to detect the expression of MDK by immunohistochemical staining. The expression of MDK in HepG2 cells was silenced by siRNA. Cell proliferation, apoptosis and invasion were detected by CCK-8, flow cytometry and Transwell, respectively. Results MDK expression was up-regulated in HCC tissues (P < 0.05). Knockdown MDK in HCC cells was significantly down-regulated cell proliferation, invasion and induced apoptosis. Conclusions MDK is over-expressed in HCC tissues. Knockdown MDK can inhibit growth and invasion on HepG2 cells.