To study the effect of the different interventional treatment on P-Glycoprotein (Pgp) in different histopathological types of primary hepatocellular carcinoma (PHC), 98 surgically and histologically verified PHC specimens were obtained. The patients included 57 patients treated by surgical resection alone and 41 patients receiving second-stage surgical resection after four kinds of interventional treatment. SABC immunohistochemical staining with a monoclonal antibody against human Pgp was used to observe the Pgp in all specimens. The positive rate of Pgp was 100 % in group of chemotherapy alone (P<0.05), 62.5 % in group of chemotherapy combined with iodized oil (P>0.05), 46.6 % in group of chemotherapy combined with iodized oil and spongia gelatini absorbens (Sga) (P>0.05), 18.18 % in group of chemotherapy combined with Ethanol-iodized-oil and Sga (P<0.05) and 52.63 % in group of surgical resection alone. The positive rate of Pgp varied with different histopathological types, with rate of clear cell PHC being the lowest, and that of poorly differentiated or undifferentiated PHC the highest. The positive rate of Pgp was increased as pathological grades increased. Overexpression of Pgp may be responsible for the intrinsic and acquired drug resistance of PHC. Multidrug resistance (MDR) varied with different histological types. Therapy of PHC should be tailored according to individual. Local chemotherapy combined with ethanol-iodized-oil and Sga embolization may become a new way to overcome MDR of PHC.