Achaete-scute homolog 1 (ASCL1) is a basic helix- loop-helix transcription factor and is essential in the differentiation of neuroendocrine cells and neural tissues. ASCL1 is frequently overexpressed in small cell lung cancer (SCLC) and plays a crucial role in the pathogenesis of SCLC. This study was conducted to identify the association between single nucleotide polymorphisms (SNPs) in ASCL1 target genes and clinical outcomes of patients with SCLC after chemotherapy. The two-hundred sixty-one patients diagnosed as SCLC were enrolled in this study. The association between 103 SNPs in 58 ASCL1 target genes and the response to chemotherapy and survival of patients with SCLC were analyzed. Among the 103 SNPs, 10 SNPs were significantly associated with the response to chemotherapy, and 19 SNPs were associated with OS in multivariate analyses. Among these, Dopa Decarboxylase (DDC) rs12666409A>T was significantly associated with both worse response to chemotherapy and worse OS (adjusted odds ratio [aOR] = 0.40, 95% CI = 0.18-0.90, P = 0.03; adjusted hazard ratio [aHR] = 1.52, 95% CI = 1.10-2.10, P = 0.01, respectively, under a dominant model). In a stage-stratified analysis, the association was significant only in the extensive stage subgroup (aOR = 0.19, 95% CI = 0.06-0.60, P = 0.01; aHR = 1.73, 95% CI = 1.16-2.56, P = 0.01, respectively, under a dominant model), but not in the limited stage subgroup. These results suggest that DDC rs12666409A>T may be useful markers for predicting the clinical outcomes of patients with SCLC undergoing chemotherapy.