Abstract: Objective To investigate mitochondrial DNA（mtDNA） mutations between different types of samples in hepatocellular carcinoma （HCC） patients. Methods The tumor tissues，adjacent tissues （≤3 cm from the tumor tissue），peripheral blood cells，and plasma of 5 patients with HCC diagnosed pathologically in the First Affiliated Hospital of Air Force Medical University were collected from September 23，2017 to December 18，2017. mtDNA copy number of tumor tissues and plasma samples were detected by whole genome sequencing. mtDNA mutations in tumor tissues，adjacent tissues，peripheral blood cells and plasma samples were analyzed by targeted next generation sequencing（NGS）. Results Whole genome sequencing results showed that the mtDNA copy number in plasma was significantly reduced compared with tumor tissues（Z＝-2.023，P＝0.008）. Targeted capture sequencing results showed that 181，180，181，179 homogeneous mutations and 33，42，3，78 heterogeneous mutations were identified in tumor tissues，adjacent tissues，peripheral blood cells and plasma samples，respectively. 10，39，and 56 specific mutation sites were detected in tumor tissues，adjacent tissues，and plasma，respectively. The frequency of mtDNA mutations in plasma was not significantly lower than that in tumor tissues（P=0.219）. Conclusion  Targeted next generation sequencing can detect mtDNA mutations in plasma samples of patients with hepatocellular carcinoma，and accurately discover the low-frequency mutations in plasma，which can be a powerful complement to tissue biopsy.

Key words: Hepatocellular carcinoma, Next generation sequencing, Mitochondrial DNA, Somatic mutation