Aloperine has been shown to exhibit tremendous pharmacological potential. The present study was designed to investigate the effects of aloperine against human liver cancer cells and to explore the underlying mechanism. The results showed significant (P < .05) upregulation of GRO alpha (GRO1 oncogene) in liver cancer tissues and cell lines. However, the expression of GRO alpha significantly (P < .05) declined in liver cancer cells treated with aloperine (5 mu M) which was concomitant with the inhibition of proliferation. Silencing of GRO alpha significantly (P < .05) inhibited the proliferation of the liver cancer via G(2)/M cycle arrest. Interestingly, aloperine also triggered G(2)/M cell cycle arrest of the liver cancer cells. Nonetheless, the growth inhibitory effects of aloperine on liver cancer cells were attenuated by GRO alpha overexpression and the cancer cells did not show the arrest of cell division. Additionally, aloperine also suppressed the migration, invasion and epithelial to mesenchymal transition of the human liver cancer cells via inhibition of GRO alpha expression. Collectively, the findings revealed growth inhibitory effects of aloperine via suppression of GRO alpha expression and point toward its therapeutic potential.