Abstract: Objective To explore the risk factors of primary liver cancer in Shunde, Guangdong, and to provide scientific basis for prevention of liver cancer. Methods A frequency-matched case-control study was conducted, including 757 liver cancer cases and 1 061 controls. The non-conditional Logistic regression model was applied to explore the potential risk factors. Results There were no significant differences in distribution of sex and age between cases and controls (P>0.05). As shown by the multivariate Logistic regression analysis, the factors associated with the risk of liver cancer included chronic hepatitis B virus (HBV) infection (OR=25.82,95% CI:18.11-36.83,P<0.001), family history of cancer (OR=2.58,95% CI:1.72-3.88,P<0.001), smoking (OR=2.92,95% CI:2.01-4.26,P<0.001), alcohol drinking (OR=1.93,95% CI:1.34-2.79,P<0.001), drinking river water or ditch pond water (OR=3.82,95% CI:2.72-5.35,P<0.001), eating raw fish (OR=2.47,95% CI:1.47-4.12,P=0.001), eating pickled food (OR=2.57,95% CI:1.86-3.55,P<0.001), tea drinking (OR=0.21,95% CI:0.14-0.30,P<0.001) and in-service status (OR=0.34,95% CI:0.23-0.50,P<0.001). Conclusions Chronic HBV infection, family history of cancer, smoking, alcohol drinking, drinking river water or ditch-pond water, eating raw fish and eating pickled food are the risk factors for primary liver cancer, while tea drinking and in-service status may be protective factors.