Objective To analyze the mortality and influencing factors of hepatobiliary cancer patients using the death data of hepatobiliary malignant tumors of Yangpu District, Shanghai, from 1974 to 2015. Methods Joinpoint regression was used to analyze the mortality trend of hepatobiliary cancer. Age-period-cohort (APC) model was employed to evaluate the effects of age and cohort factors on the mortality rate of hepatobiliary cancer. Results From 1974 to 2015, a total of 9 866 liver cancer deaths were reported in Yangpu District, with a male to female ratio of 2.7:1; and the crude mortality rate and standardized mortality rate were 23.09/100 000 and 18.87/100 000, respectively. A total of 2 173 biliary tract cancer deaths were reported, with a male to female ratio of 1:1.7; and the crude mortality rate and standardized mortality rate were 5.04/100 000 and 3.82/100 000, respectively. Joinpoint regression analysis showed that the standardized mortality rate of liver cancer decreased from 1974 to 2015, while that of biliary tract cancer increased. In APC model, the overall mortality risk of liver cancer and biliary tract cancer increased with the increase of age. The mortality rates of liver cancer and biliary tract cancer were increased in the population born before 1930. The mortality rates of the male liver cancer and the male and female biliary tract cancer were decreased in the population born between 1930 and 1949. The mortality rate of liver cancer was increased in the females born after 1949. Conclusion From 1974 to 2015, the mortality rate of liver cancer has a decreasing trend in Yangpu District, Shanghai, and the mortality rate of male is higher than that of female. The mortality rate of biliary tract cancer shows an increasing trend, and the mortality rate of female is higher than that of male. The mortality rates of liver cancer and biliary tract cancer associated with aging factors have increased. Exposure factors have a consistent effect on liver cancer and biliary tract cancer, which may be related to socioeconomic factors at that time.