OBJECTIVE To explore the correlation of chemotherapy efficacy in malignant lymphomas with the expression level of multidrug resistance gene 1 (mdr1) mRNA, multidrug resistance-associated protein (MRP), and P-glycoprotein (P-gp). METHODS Using the methods of semi quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and flow cytometry (FCM), a prospective research was performed to detect the expression levels of molrl gene, MRP gene, and p-gp in the lymph nodes of 23 untreated first visit (HD1, NHL 22) and 23 recurrent (HD 5, NHL 18) lymphoma patients. Eight normal human lymph nooles were used as controls. RESULTS The expression levels and positive rates of mdr1 and P-gp in recurrent patients were higher than those in untreated patients (P < 0.001). There was no difference in MRP gene expression level and positive rate between recurrent and untreated patients (P > 0.05). The chemotherapy effective rates were lower in mdr1 gene and P-gp positive expression patients (33.33% and 26.67%) than in negative expression patients (85.71% and 83.87%) (P < 0.001). Relevant analysis showed that there was a significant relevance in expression level between mdr1 gene and P-gp (r = 0.296 3, P < 0.05), but there was no correlation between mdr1 and MRP or between MRP and P-gp (r = 0.072 3, P > 0.05; r = 0.081 8, P > 0.05). CONCLUSIONS mdr1 gene and P-gp expression levels are dominant mechanisms of clinical drug resistance of lymphomas, whereas, MRP gene appears to play no role in that course. mdr1 gene and P-gp expression levels are relevant to chemotherapy efficacy, however, MRP gene expression level seems to have no impact on it.