Single-nucleotide polymorphism of CLPTM1L-rs401681(C > T) at the 5p15.33 locus is significantly associated with cancer risk as reported in genome-wide association studies, but the reported studies for non-melanoma skin cancer (NMSC) are inconclusive. To assess the association between rs401681[C] allele and NMSC risk, we performed this meta-analysis with four case-control studies involving 5,469 cases and 39,715 controls. Our meta-analysis showed that rs401681[C] allele was associated with NMSC susceptibility in the overall subjects (C vs. T, OR 1.13, 95 % CI 1.07-1.20). In the stratified analysis, the rs401681[C] allele confers susceptibility in Icelanders (C vs. T, OR 1.15, 95 % CI 1.06-1.26) and non-Icelanders (C vs. T, OR 1.13, 95 % CI 1.03-1.24). In the subtype analysis, we found that rs401681[C] allele was a risk factor for BCC, but not SCC in the overall subjects.