Curcumin is the most abundant derivative of turmeric rhizome. Although studies have proved that curcumin could inhibit the growth of tumors, its specific molecular mechanism has not yet been fully elucidated. This study aims to systematically elaborate the mechanisms of curcumin against hepatocellular carcinoma. The anti-tumor effect of curcumin was determined by the cell viability test. Flow cytometry was applied to examine the cell cycle and the apoptosis of cancer cells, and the cancer cell migration was detected by wound healing experiments. The expressions of signal transducers and activators of transcription 3 (STAT3), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF-1α) in cancer cells were examined by immunostaining and analyzed by the Image J analysis system. After treatment with curcumin, the apoptosis ratio of HepG2 cells increased significantly (P < 0.05). The proliferation of cancer cells was arrested at the S-phase cell cycle, and the migration of cancer cells was inhibited by the increasing concentration of curcumin, together with the decreasing expressions of STAT3, VEGF, and HIF-1α signaling pathways. The results indicate that curcumin could effectively inhibit the growth and migration of hepatocarcinoma cells by inducing cancer cell apoptosis, blocking the cancer cell cycle in the S phase, and reducing the expression of STAT3, VEGF, and HIF-1α signaling pathways.