To study the anticancer activities of curcumin on human hepatocarcinoma cell line Sk-hep-1 and its related molecular mechanism which has not been elucidated. In the present study,we showed that curcumin inhibited proliferation of Sk-hep-1 cells in a dose-dependent manner through MTF assay. The effect of curcumin on apoptosis in Sk-hep-1 cells was investigated by DAPI staining and the various apoptosis was observed in hepatocarcinoma cell lines Sk-hep-1, HepG2 and Hep3B, but not in normal liver cell line Chang's liver with curcumin treatment. Cell cycle analysis results showed that curcumin treatment resulted in dramatic accumulation of Sk-hep-1 cells at the G0/G1 or G2/M phase. The effect of curcumin on the expression of anti-apoptosis genes (Survivin and BCl-xL) and drug resistance genes (DRG2 and MDR1) was studied by reverse transcription-polymerase chain reaction (RT-PCR). The expression of MDR1 mRNA was significantly decreased in Sk-hep-1 cells treated with curcumin, while no alterations in the amount of DRG2 and anti-apoptosis genes' mRNA levels were found. These results indicate that curcumin is able to inhibit proliferation and induce apoptosis in Sk-hep-1 cells and it may cause by down-regulating the expression of MDR1 mRNA.