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Objective: To study the clinical significance and relationshipbetween c-fms oncogene and hepatocellular carcinogenesis, to further clarify the occurring mechanism of hepatocellular carcinoma (HCC). Methods: PCR-SSCP technique was used to analyse mutation of c-fms oncogene in 30 cases of HCC tissues. Sequencing the PCR products after cloning to prove the mutations, meanwhile the relationship between c-fms mutations and clinical pathology of HCC was investigated. Results: Two abnormal single strands were observed in l0% (3/30) HCC tissues from c-fms DNA corres-ponding to 301st codon of c-fms amino acids. PCR products of abnormal single strands were sequenced after cloning, it demonstrated that there was transition of T? C at nucleic acid 14855 of c-fms DNA, which corresponded to transition of Leu (TTG)? Ser (TCG) at 301st codon of c-fms amino acids. The mutation was related to malignant degree and type of HCC tissues as well as patient’s age. Conclusion: Mutation of c-fms codon at site 301 implied a molecular mechanism contributing to hepatocellular carcinogenesis.