Background: We conducted a systematic review and meta-analysis of interferon regulatory factor 6 and 8q24 polymorphisms with nonsyndromic cleft lip with/without cleft palate (NSCL/P). Methods: Data extraction was independently performed by two reviewers. Genotypic effects of four polymorphisms from 31 studies were pooled separately by ethnicity using a mixed-effect logit model with accounting for heterogeneity. Results: For rs2235371, AA and GA carried, respectively, 51% (95% confidence interval [CI], 37%-61%) and 42% (95% CI, 32%-50%) lower risks of NSCL/P than GG genotypes in Asians, but these genotypes were not significant in Caucasians. For rs2013162, only AA was significant, that is, carried 0.65 (95% CI, 0.52-0.82) times lower odds than CC in Caucasians but not for Asians. For rs642961, AA and GA genotypes, respectively, carried 2.47 (95% CI, 1.41-4.35) and 1.40 (95% CI, 1.12-1.75) times higher odds in Asian, and 2.03 (95% CI, 1.52-2.71) and 1.58 (95% CI, 1.37-1.82) times higher odds in Caucasians compare with GG genotypes. For rs987525, AA and CA genotypes carried 2.27 (95% CI, 1.43-3.60) and 1.34 (95% CI, 1.02-1.77) times higher odds in Asian, and 5.25 (95% CI, 3.98-6.91) and 2.13 (95% CI, 1.82, 2.49) times higher odds in Caucasians, and 1.42 (95% CI, 1.10-1.82) and 1.28 (95% CI, 1.09-1.50) times higher odds in mixed ethnicities compared with CC genotypes. These variant effects remained significant based on applying Bonferroni corrected-thresholds, except in the mixed ethnicity. Conclusion: We show robust variant effects in NSCL/P. Considering them with other genes and risk factors might be useful to improve prediction of NSCL/P occurrence.