Objective To explore the causal association between radiation exposure and risk of head and neck cancer using Mendelian randomization (MR) method. Methods Genome-wide association studies of radiation exposure and head and neck cancer in the public database IEU OpenGWAS were identified, and single nucleotide polymorphisms (SNPs) were screened as instrumental variables. Two-sample MR analyses were performed using random-effect inverse variance weighted (IVW), fixed-effect IVW, weighted median, and MR-Egger methods to assess the causal association between radiation exposure and risk of head and neck cancer. Outliers were tested using the MR-PRESSO method, and heterogeneity was assessed using the Cochran Q test. MR-Egger regression intercept was utilized to detect gene-level pleiotropy, and a leave-one-out sensitivity analysis was conducted to evaluate the robustness of the study results. Results96 valid SNPs were included as instrumental variables. The analysis results of random-effect IVW method, fixed-effect IVW method, and weighted median method all showed that radiation exposure was associated with an increased risk of head and neck cancer [odds ratio and 95% confidence interval: 1.139 (1.065, 1.218), 1.139 (1.068, 1.215), and 1.141 (1.039, 1.253); P<0.05]. Heterogeneity testing did not reveal significant heterogeneity, MR-Egger regression analysis did not find gene level pleiotropy, and the leave-one-out method did not find a single SNP significantly affecting the overall estimation results. Conclusion Radiation exposure increases the risk of head and neck cancer, but this conclusion still needs further validation in more high-quality, large sample studies.