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AIM: To study the deletion of mitochondiral DNA in hepatocellular carcinoma and hepatocellular nodular hyperplasia and its significance in the development of cancer.METHODS: Deleted mtDNA (CD-mtDNA) and wild type mtDNA (WT-mtDNA) were quantitatively analyzed by using real-time PCR in 27 hepatocellular carcinomas (HCC)and corresponding noncancerous liver tissues and 27hepatocellular nodular hyperplasiae (HNH).RESULTS: A novel CD (4 981 bp) was detected in 85%(23/27) and 83%(22/27) of HCC and HNH tumor tissues,respectively, which were significantly higher than that in paired noncancerous liver tissues (57%, 15/27) (P＜0.05).The CD/WT-mtDNA ratio in HCC tumors was 0.00092(median, interquartile range, 0.0001202-0.00105), which was significantly higher than that in paired noncancerous liver tissues (median, 0.000, quartile range, 0-0) (P=0.002,Mann-Whitney Test), and was 25 of times of that in HNH tissues (median, 0.0000374, quartile range, 0-0.0004225)(P=0.002, Mann-Whitney test).CONCLUSION: CD-mtDNA mutation plays an important role in the development and progression of HCC.