Objective To explore effect and mechanism of down-regulation of Derlin-1 on the chemosensitivity of nasopharyngeal carcinoma cell (NPC) CNE-2Z.Methods The NPC tissues and adjacent normal tissues were collected from 10 NPC patients, and the content of Derlin-1 mRNA in the tissues was detected by real-time quantitative polymerase chain reaction (RT-qPCR). The CNE-2Z cells were divided into blank control group (control group), negative control group (NC group), knockdown group (si-Derlin-1 group). RT-qPCR method was adopted to detect the expression of Derlin-1 mRNA in NPC, the tetramethylazazole blue (MTT) method to detect the proliferation of cells of the three groups at different cisplatin concentrations, Annexin V-FITC/PI double staining method to detect the apoptotic rate of cells of the three groups at cisplatin concentration of 5 μmol/L, Transwell to detect cell invasion and migration ability of the three groups at the cisplatin concentration of 5 μmol/L. RT-qPCR, Western blot were used to detect relative mRNA and protein expressions of Bcl-2, Bax, matrix metalloproteinase (MMP)2, and MMP9.Results RT-qPCR results showed that the relative expression of Derlin-1 mRNA in NPC tissues was significantly lower than that in adjacent normal tissues, and the difference was statistically significant (P<0.05). Compared with the control group and NC group, Derlin-1 mRNA in the si-Derlin-1 group was significantly decreased, and the difference was statistically significant (P <0.05). The results of MTT method revealed that the cell proliferation rate in the si-Derlin-1 group was significantly lower than those of the control group and NC group, and the difference was statistically significant (P<0.05). Annexin V-FITC/PI double staining showed that the apoptosis rate of si-Derlin-1 group was (29.65±2.35)% when the cisplatin concentration was 5 μmol/L, which was elevated compared with the control group (13.24±1.43)% and the NC group (15.09±1.32)%, the differences were statistically significant (P<0.05). The cell migration rate and invasion rate in the Derlin-1 group were (20.15±2.20)% and (22.33±3.5)% respectively, which were significantly decreased compared with those of the control group [(100±1.3)%, (99±2.43)%] and the NC group [(96.72 ±3.22) %, (94.44 ±1.21)%], and the differences were statistically significant (F migration rate=1080.610，P=0.000),(F invasion rate=848.590, P=0.000). RT-qPCR results showed that compared with the control group and NC group, the expression of mRNA of the apoptosis inhibitor Bcl-2 in the si-Derlin-1 group decreased, the expression of mRNA of apoptosis-inducing factor Bax was up-regulated, and the relative expressions of mRNA of migration-related factors MMP2 and MMP9 were significantly decreased, and the differences were statistically significant (all P<0.05); Western blot results showed that compared with the control group and NC group, the expression of apoptosis-inhibiting protein Bcl-2 in si-Derlin-1 group was decreased, and the expression of apoptosis-inducing protein Bax was up-regulated, the relative expression of MMP9 protein was significantly decreased, and the differences were statistically significant (all P<0.05).Conclusion Nasopharyngeal carcinoma; Derlin-1; Chemosensitivity; Apoptosis; Invasion and migration