We studied the mechanisms involved in the drug resistance of C6/ADR and compared the reversal effects of XIAP and MDR1 ASO used in combination and separately. Reverse transcription-PCR and Western blot were applied to detect the mRNA and protein levels, respectively. The results showed that XIAP and MDR1 ASO used separately could down-regulate the levels of XIAP and MDR1 in C6/ADR cells, respectively. XIAP and MDR1 ASO used in combination did not enhance the inhibition expression of XIAP and MDR1 of C6/ADR cells. The apoptosis of co-transfection group was significantly higher than XIAP ASO (P < 0.05). When used in combination the sensitivity of C6/ADR cells to ADR was increased significantly compared with XIAP or MDR1 ASO used separately (P < 0.05). The results indicated that both XIAP and MDR1 were involved in the drug resistance of C6/ADR cells. The sensitivity to ADR could be enhanced significantly when XIAP and MDR1 ASO used in combination.