Objective To investigate the expression and relationship between hepatocyte cell adhesion molecule (hepaCAM) protein and some multidrug resistance proteins in renal carcinoma tissue. Methods Expressions of hepaCAM, multidrug resistance associated protein (MRP), P-glycoprotein (P-gp), lung resistance protein (LRP), and topoisomerase Ⅱ (TOPO Ⅱ) protein were detected by immunohistochemistry in different areas of human renal cell carcinoma tissues and their relationships were analyzed. Results In the peripheral zone of renal tumor, hepaCAM, MRP, P-gp and LRP protein were showed positive expression. In the central region of the renal tumor, the expressions of hepaCAM, P-gp and LRP were negative or weakly positive, while the expressions of MRP and TOPO Ⅱ protein were positive. The expressions of MRP and TOPO Ⅱ protein in the central region of tumor were stronger than those in the peripheral zone of tumor (31.23±5.67 vs. 23.89±4.56; 45.66±2.34 vs. 5.23±0.66), with statistically significant differences (t=-6.20, P=0.00; t=-100.16, P=0.00). While the expressions of other proteins (hepaCAM, P-gp and LRP) in the central region of tumor were weaker than those in the peripheral zone of tumor (3.21±1.12 vs. 27.25±2.23; 2.34±0.33 vs. 51.23±3.45; 4.22±1.78 vs. 44.23±1.45), with statistically significant differences (t=60.87, P=0.00; t=90.35, P=0.00; t=107.18, P=0.00). Correlation analysis showed that the expression of hepaCAM protein in the central region of renal carcinoma was related with the expression of MRP protein (r=0.94, P=0.01), but it was not related with the expressions of P-gp, LRP and TOPO Ⅱ protein (r=0.22, P=0.44; r=0.14, P=0.80; r=0.34, P=0.07). Conclusion The expression of hepaCAM protein in renal carcinoma may be related to tumor drug-resistance. Key words: Kidney neoplasms; Cell adhesion molecules; Multidrug resistance-associated proteins