In the present study, we investigated the mechanisms of curcumin against hepatocellular carcinoma and examined whether curcumin could interfere with the HIF-1α/STAT3/VEGF signal transduction pathways, induce apoptosis, and arrest the cell cycle against the proliferation of cancer cells, further confirming the multiple anti-tumor bioactivities of curcumin. This evidence concerns the gene STAT3 and cancer.