Objective: To observe the expression changes of the clock genes in hepatocellular carcinoma (HCC) cells under cobalt chloride (CoCl2)-induced hypoxic condition. Methods: HCC Huh7 cells were exposed to different concentrations (0, 50, 100 and 200 μmol/L) of CoCl2 for 24 h, and then, the protein expressions of hypoxia-inducible factor-1α (HIF-1α) in the cells were determined by Western blot analysis and the mRNA expressions of the clock genes that included CLOCK, BMAL1, Per1, Per2, Per3, Cry1, Cry2 and CKIε in the cells were detected by real-time PCR method. Results: The results of Western blot showed that there was no visible HIF-1α protein expression in the Huh7 cells (0 μmol/L CoCl2), while the HIF-1α protein expressions were clearly seen in the Huh cells treated with each concentration of CoCl2, and the expression level was increased with CoCl2 concentration. The results of real-time PCR showed that the mRNA levels of Bmal1, Per1 and Cry2 were up-regulated while mRNA levels of CLOCK, Cry1, Per2 and CKIε mRNA levels were down-regulated significantly after CoCl2 treatment, and all presented a CoCl2 concentration-dependent manner (all P<0.05). Conclusion: Hypoxia microenvironment may be one of the causes for the abnormal expression of clock genes in HCC cells.