The host immune system plays a crucial role in multiple types of cancer, including non-small-cell lung cancer (NSCLC). Transporter associated with antigen processing (TAP) protein heterodimer complexes might promote intracellular antigen peptide binding with class I major histocompatibility complex (MHC-I) molecules, and in recent years, TAP1 and TAP2 have been reported to be associated with multiple cancer risks. In the current study, we investigated the association of single-nucleotide polymorphisms (SNPs) in TAP1 and TAP2 with NSCLC in a Han Chinese population. Six and seven TAP1 and TAP2 SNPs, respectively, were genotyped and analysed in healthy controls and NSCLC patients. Based on our data, none of the six SNPs in TAP1 is associated with NSCLC risk (P > 0.0038). However, rs2228396 alleles in TAP2 were significantly different between NSCLC patients and healthy controls, and the A allele might be associated with an increased risk of this cancer (P = 0.001, OR = 1.65, 95%CI: 1.23 similar to 2.21). Moreover, the genotype frequencies of rs2228396 were significantly different between patients and healthy con-trols (P = 7 x 10(-4)). Additionally, TAP2 rs241441 alleles exhibited a trend of difference between NSCLC patients and healthy controls, with the C allele possibly being associated with increased risk of NSCLC (P = 0.013; OR = 1.30, 95%CI: 1.06 similar to 1.60). Moreover, the genotypes of rs241441 in TAP2 showed a signif-icant difference between NSCLC patients and healthy controls (P = 1 x 10(-4)). In haplotype analysis, the TAP2 SNP haplotype (CAC, TAP2*0102) was significantly associated with increased NSCLC risk in the Han Chinese population (P = 0.003; OR = 1.57, 95%CI: 1.17 similar to 2.10). Our results indicate that TAP2 SNPs (rs2228396 and rs241441) have a potential role in NSCLC pathogenesis. (C) 2021 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.