Objective To evaluate the clinical therapeutic effect with microspheres embolization for giant hepatocellular carcinoma(HCC). Methods A prospective study was performed for 156 HCC patients needed for TACE, then randomly signed them into group M (embolized by microspheres alone), group L (embolized by lipiodol alone) and group M + L (embolized by microspheres combined with lipiodol). TACE of group M was performed by 300-700 μm microspheres. Group L selected lipiodol alone to embolize. While group M + L were embolized by about 1/3-1/2 lipiodol of total embolized volume and then microspheres feeding individual tumor vessels. Stoped the procedure when caused terminal vessel blockade. Before and after therapy, patients'liver function, serum α-fetoprotein level (AFP), responses of tumor, complications related to embolization and survive rates of 180 days and 360 days were analyzed among three groups.Enumeration data such as survive rates and positive response were compared by χ2 test, while measurement data were analyzed by one-way classification. Results The positive response (CR + PR) of group M was 38.5% (20/52)and (CR + PR + SD)73. 1% (38/52). Survive rates of 180 days and 360 days were 88. 5% (46/52) and 82. 3% (43/52). While those of group L were 42. 3% (22/52) ,76.9% (40/52),86.5%(45/52), 75.0% (39/52) and group M + L were 55. 8 % (29/52), 88.5 % (46/52), 94. 2% (49/52),86. 5％ (45/52). Significant difference of survival rates and total effective between group M + L and M,M + L and L was found(χ2 = 6. 27,6. 16, P ＜ 0. 05). At the same time adverse responses of incidence and persis time such as febricity, nausea and vomit, hepatic pain were more lower in group M + L and group M.Three groups febricity rate were 63.4% (33/52), 86. 5% (45/52) and 69. 2% (36/52), nausea and vomit were 67.3 % (35/52) ,84. 6% (44/52) and 76. 9% (40/52), hepatic pain were 59. 6% (31/52), 86. 5 %(45/52), 73. 1% (38/52) (χ2 = 6.55, 6. 22, 6. 90, P ＜ 0. 05). Conclusion Embolization with microspheres can get longer and more effective treatment. TACE with microspheres and lipiodol for embolizing HCC was more effective than with Microspheres or lipiodol alone.