〔Abstract〕 Objective To explore the influences of activating transcription factor 4(ATF4) on the proliferation, migration and apoptosis of hepatocellular carcinoma(HCC) and itsmolecular mechanism.Methods Expression of ATF4 andthe hexokinase domain component 1(HKDC1) were down-regulated in HepG2 and Huh7 cells by RNA interference technique. In HCC cell lines, CCK-8, clone formation, wound-healing assay and flow cytometry apoptotic analysis were used to observe the changes in the proliferation, migration and apoptosis of HCC after transfection, and the expressions of ATF4,HKDC1 and apoptosis-related proteins Bcl-2 and Bax in hepatocellular carcinoma cells were determined by Western blot. Results Functional studies had shown that knockdown of ATF4 and HKDC1 not only led to an increase in cell apoptosis and a decrease in cell proliferation but also inhibited the cells' abilities of migration; ATF4 silencing could inhibit the expression of HKDC1 protein. Conclusion ATF4 may play a role in the progression of hepatocellular carcinoma by regulating the expression of HKDC1 protein,and HKDC1 may be a potential target of therapeutic intervention for HCC.