Abstract: Objective To evaluate the application value of cfDNA detection combined with liver MRI in the screening of hepatocellular carcinoma. Methods 126 patients with highly suspected liver cancer were selected as the research objects. According to the results of pathological examination, 82 of them were hepatocellular cancer patients （hepatocellular cancer group） and 44 were benign tumor patients （benign group）. The two groups of cfDNA, RNaseP （cfDNA reference gene） gene copy, liver function indexes alanine transaminase （ALT）, aspartate transaminase （AST）, alkaline phosphatase （ALP） and tumor marker levels （alpha-fetoprotein （AFP）, carcinoembryonic antigen （CEA）, carbohydrate antigen （CA199） were compared. The relationship between cfDNA levels and pathological parameters of hepatocellular carcinoma was studied. And the diagnostic efficacy of RNaseP gene copy combined with MRI in hepatocellular carcinoma was evaluated. Results The cfDNA, RNaseP gene copy, AFP, CEA, CA199, ALT, AST and ALP of the liver cancer group were significantly higher than those of the benign group, and the differences were statistically significant （P<0.05）. The Child-Pugh score, end-stage liver disease model score, tumor size, metastasis, and alcoholic hepatitis positive of liver cancer patients were statistically significant in the low cfDNA （<20 ng/mL） group and high cfDNA （≥20 ng/mL） group Difference （P<0.05）. The sensitivity of RNaseP gene copy combined with MRI in the diagnosis of hepatocellular cancer was significantly higher than that of RNaseP gene copy （χ²=9.043, P=0.003） and MRI （χ²=7.12, P=0.006）. Conclusions The cfDNA of patients with hepatocellular carcinoma was significantly increased. The level of cfDNA was related to the pathological parameters of hepatocellular carcinoma. cfDNA reference gene RNaseP detection combined with MRI had better application value for screening of hepatocellular carcinoma.