〔Abstract〕 Objective To explore the role of miR-146 a-5 p in the drug resistance mechanism of small cell lung cancer(SCLC). Methods The expression levels of miR-146 a-5 p in drug-resistant SCLC cell lines(H69-AR) and sensitive cell lines(H69) were tested by qRT-PCR to explore the correlation between miR-146 a-5 p and SCLC drug resistance. MiR-146 a-5 p was upregulated or inhibited by lentivirus vector stably transfected with miR-146 a-5 p mimic or miR-146 a-5 p inhibitor, respectively. The biological effects of miR-146 a-5 p on SCLC cell lines were verified by CCK-8 method and Nick experiment. The target gene of mir-146 a-5 p was predicted by searching related literatures and using the most authoritative software in biology. The correlation between miR-146 a-5 p and the predicted target genes was detected by western-blot, real-time quantitative qPCR and other methods. Results The expression level of miR-146 a-5 p in H69-AR compared with H69 cell line was(1 ∶22.70)(P<0.05). The potential target genes of miR-146 a-5 p were predicted by biological software to be interleukin-1 receptor-related kinase 1(IRAK1) and tumor necrosis factor receptor-related factor 6(TRAF6). The expression levels of mIRAK1 and mTRAF6 in H69-AR relative to H69 cells were significantly different(4.92 ∶1.00 and 2.76 ∶1.00)(P<0.05). After transfection of miR-146 a-5 p mimic in H69 AR cell line, compared with the control group, the cell inhibition rate increased, the migration rate slowed down, and the expression levels of mIRAK1 and mTRAF6 decreased to(1.00 ∶14.55) and(1 ∶3.20), respectively.The expressions of IRAK1 and TRAF6 decreased to(0.24 ∶1.00) and(0.31 ∶1.00)(P<0.05). After transfection of miR-146 a-5 p inhibitor in H69 cell line, compared with the control group, the cell inhibition rate decreased and the migration rate increased. At the same time, the expression levels of mIRAK1 and mTRAF6 increased to(10.86 ∶1.00) and(4.64 ∶1.00), respectivelywhile the expressions of IRAK1 and TRAF6 increased to(4.76 ∶1.00) and(3.96 ∶1.00), respectively(P<0.05). Conclusion MiR-146 a-5 p inhibits SCLC resistance by IRAK1 and TRAF6 genes.