The studies recommended the relationship between lots of polymorphisms with the head and neck cancers (HNCs) risk. Herein, we reported the association between the CYP1A1 MspI polymorphism and the risk of HNC in an updated meta-analysis. The PubMed/MEDLINE, Web of Science, Cochrane Library, and Scopus databases were searched until March 31, 2021, without any restrictions. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to assess a relationship between CYP1A1 MspI polymorphism and the HNC risk based on five applied genetic models by RevMan 5.3 software. Other analyses (sensitivity analysis, meta-regression, and bias analysis) were performed by CMA 2.0 software. Trial sequential analysis (TSA) was done by TSA software (version 0.9.5.10 beta). Among the databases and other sources, 501 recorded were identified that at last, 29 studies were obtained for the analysis. The pooled ORs were 1.28 (95%CI 1.09, 1.51; P = 0.003), 1.68 (95%CI 1.16, 2.45; P = 0.007), 1.24 (95%CI 1.03, 1.50; P = 0.02), 1.26 (95%CI 1.07, 1.48; P = 0.005), and 1.66 (95%CI 1.27, 2.16; P = 0.0002) for allelic, homozygous, heterozygous, recessive, and dominant models, respectively. Therefore, the m2 allele and m1/m2 and m2/m2 genotypes had significantly increased risks in HNC patients. With regards to stable results and enough samples, the findings of the present meta-analysis recommended that there was an association between CYP1A1 MspI polymorphism and the HNC risk.