Radioresistance is a major obstacle to the treatment of human nasopharyngeal carcinoma (NPC). Emerging evidence has demonstrated that miRNAs are involved in cancer therapy resistance. Our research group established the radioresistant NPC cell line CNE2R derived from the CNE2 cell line, and demonstrated that irradiation-induced miR-205 determined the resistance of NPC through directly targeting PTEN. However, specific inhibitors targeting miRNAs are largely undetermined. SZ-685C was expected to abrogate the radioresistance of CNE2 cells through the miR-205‑PTEN-Akt pathway. SZ-685C exhibited a similar cytotoxic effect on both cell lines, and we demonstrated that both intrinsic and extrinsic pathways were activated by SZ-685C in the cell lines. Importantly, the miR-205-PTEN-Akt pathway was the key cell signaling pathway activated in the CNE2R cells upon SZ-685C treatment; however, the Stat3-Jab1-p27 pathway might participate in the pro-apoptotic effect in CNE2 cells but not in CNE2R cells. SZ-685C is a promising anticancer agent for treatment of NPC, and it exhibited pro-apoptotic activity in both radiosensitive and radioresistant NPC cells. Although the mechanisms between the two cell lines were not identical, the pro-apoptotic effects were similar between the two cell lines.