BACKGROUND: The surgical resection rate of pdmary hepatic carcinoma is low, thus, the local treatment arose more attention. Microwave coagulation therapy can inactivate rather than kill the hepatic carcinoma ceils. Slow-release chemotherapy has been used in treating primary hepatic carcinoma because it can form local high concentrations and last for a long time. OBJECTIVE: To observe the therapeutic effect of epirubicin-loaded chitosan microspheres combined with microwave coagulation on treating hepatocellular carcinoma in mica. METHODS: Epirubicin-loaded chitosan microspheres were prepared by using emulsion-chemical cross linking technique. The surface morphology and particles size of chitosan microspheres were observed by scanning electron microscope. Ultraviolet speotrophotometer was used to analyze the entrapment efficiency, entrapment efficiency and cumulative release rates of epirubicin-loaded chitosan microspheres. Totally 24 mice with transplanted subcutaneous H22 HCC were divided into 4 groups, which were respectively treated by microwave coagulation therapy, intratumoral injected with physiological saline after microwave coagulation therapy, intratumoral injected with epirubicin after microwave coagulation therapy, intratumoral injected with epirubicin-ioaded chitosan microspheres after microwave coagulation therapy. The tumor inhibitory rate was calculated. RESULTS AND CONCLUSION: The average diameter of chitosan microsphere was 105 μm, with uniformed particle diameter. The ratio of drug loading was 11% and the entrapment was 80%. The in vitro drug cumulative release rate was 84% after 2 weeks. The tumor inhibitory rates of the microwave coagulation combined with physiological saline, epirubicin, and drug carried microspheres groups were 8%, 20%, and 47%. It suggested that chitosan microsphere is a safe and effective slow-release dosage form, which exhibits strong anti-tumor effect when combined with microwave treatment.