Objective To measure the expression of Caspase-3 and P-gp in hepatocellular carcinoma (HCC) and adjacent tissues, and to examine these two proteins' relationships with HCC clinical and pathological characteristics and the associations between the two proteins. Methods The expression of Caspase-3 and P-gp were measured in 50 HCC tissues and adjacent tissues by EnvisionTM immunohistochemistry. HCC clinic and pathological characteristics and follow-up data were also collected and analyzed. Results The expression of Caspase-3 in HCC tissues was significantly lower than that in adjacent tissues(P <0.05). The expression of Caspase-3 in HCC tissues was significantly associated with HCC's Edmonson grade and the presence of hepatitis envelope(P <0.05). On the other hand, the expression of P-gp in HCC tissues was significantly higher than that in adjacent tissues( P <0.05 ). P-gp expression in HCC tissues was significantly correlated with HCC's Edmonson grade and the presence of cirrhosis(P < 0.05 ). The expression of Caspase-3 and P-gp was negatively correlated ( r = - 0. 600,P = 0.000). A better prognosis was observed among HCC patients with either positive Caspase-3 expression or negative P-gp expression(P < 0.05). Conclusion Caspase-3 may promote apoptosis and inhibit the development of HCC, while P-gp may have an anti-apoptosis function and play a role in HCC's drug resistance. P-gp can inhibit the function of Caspase-3 and an absence or low expression of Caspase-3 may be related to apoptosis resistance and multidrug resistance.