Background: A common single nucleotide polymorphism (SNP), rs10795668, located at 10p14, was first identified to be significantly associated with risk of colorectal cancer (CRC) by a genome-wide association study (GWAS) in 2008; however, another GWAS and following replication studies yielded conflicting results. Methods: We conducted a case-control study of 470 cases and 475 controls in a Chinese population and then performed a meta-analysis, integrating the current study and 9 publications to evaluate the association between rs10795668 and CRC risk. Heterogeneity among studies and publication bias were assessed by the χ2-based Q statistic test and Egger's test, respectively. Results: In the case-control study, significant association between the SNP and CRC risk was observed, with per-A-allele OR of 0.71 (95%CI: 0.54–0.94, P = 0.017). The following meta-analysis further confirmed the significant association, with per-A-allele OR of 0.91 (95%CI: 0.89–0.93, Pheterogeneity>0.05) in European population and 0.86 (95%CI: 0.78–0.96, Pheterogeneity <0.05) in Asian population. Besides, sensitivity analyses and publication bias assessment indicated the robust stability and reliability of the results. Conclusions: Results from our case-control study and the followed meta-analysis confirmed the significant association of rs10795668 with CRC risk. [ABSTRACT FROM AUTHOR]