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Objective: To explore the effects of matrine on HCCR1 and HCCR2 expression in cultural human hepatocellular carcinomas (HCC) cells at the level of gene and protein. Methods: Three methods, representational difference analysis(RDA) of cDNA, microarrays and fluorescence in situ hybridization (FISH) were used to detect levels of mRNA and protein expression of HCCR1 and HCCR-2 before and after treatment of matrine. Results: Matrine had inhibitory effect on the mRNA and protein expression of HCCR1 and HCCR2 in cultural HCC cells. Conclusion: Matrine has inhibitory effect on gene transcription, protein expression of HCCR1 and HCCR2 in cultural HCC cells.