Objective:To analyze the causal relationship between lifestyle-based factors and the occurrence and development of hepatobiliary malignancies by Mendelian randomization study method,and to provide the potential clinical evidence for the prevention and treatment of hepatobiliary malignancies.Methods:The data from large-scale,independent genome-wide association studies(GWAS)were selected,and seven-step inclusion criteria for the instrumental variable screening were set up.The exposure lifestyles included the percentage of carbohydrate intake,percentage of fat intake,percentage of protein intake in the diet,coffee intake,weekly alcohol consumption times,leisure electronic screen exposure time,moderate to vigorous intensity physical activity(MVPA)during leisure time,sedentary behavior at work,age at first smoking,daily smoking quantity,current smoking status,and past smoking status,totaling 12 phenotypes.The primary analysis method used was the random effect model of the inverse variance weighted(IVW)method,and the heterogeneity was detected by Cochrane's Q test and the horizontal pleiotropy was detected by MR-Egger intercept method.Results:The current smoking status was significantly positively correlated with the increasing risk of extrahepatic cholangiocarcinoma(OR=1.607,95%CI:1.113-2.322,P=0.011).Higher coffee intake was causally linked to a higher risk of liver cancer and intrahepatic cholangiocarcinoma(OR=1.000,95%CI:0.999-1.000,P=0.012).In the physical activity,more MVPA was associated with the lower risk of liver cancer and intrahepatic cholangiocarcinoma(OR=0.998,95%CI:0.996-0.999,P=0.002).The Cochrane's Q test results showed that there was mild heterogeneity between MVPA and extrahepatic cholangiocarcinoma(Q=18.354,P=0.049)as well as the percentage of protein intake and intraphepatic cholangiocarainoma(Q=12.715,P=0.026),and the MR-Egger intercept method results showed there was no horizontal pleiotropy.Conclusion:There is a causal relationship between current smoking status and extrahepatic cholangiocarcinoma,and there is a causal relationship between more MVPA and the lower risk of liver cancer and intrahepatic cholangiocarcinoma.Education on smoking and physical activity for the patients may offer potential benefits for the prevention of hepatobiliary malignancies.