Atopic dermatitis (AD) accounts for a large proportion of the burden of skin disease, with a prevalence of around 10% among adults worldwide. In addition, systematic reviews and meta-analyses have found that AD is associated with cancer risk at several sites; if found to be causal this could highlight potential treatment targets to reduce cancer risk.To assess the potential causative link between AD and 14 site-specific cancers in a two-sample randomization study.From the largest genome-wide association study (GWAS) of AD (10,788 cases and 30,047 non-cases), genetic variants highly associated (P < 5 × 10-8 ) with AD in the European population were selected as instrumental variables (IVs). Data from large cancer consortia, as well as the UK Biobank study (n=442,239) and the FinnGen study (n=218,792), were employed to assess genetic associations with 14 site-specific cancers and overall cancer. A set of complementary approaches and sensitivity analyses were carried out to examine the robustness of our results. In addition, associations for the same cancer site from different data sources were combined using meta-analyses.We discovered no strong causal evidence of AD on the risk of overall cancer, with effect estimates close to zero. After Benjamini-Hochberg correction, the inverse variance weighted method indicated no association between AD and overall cancer risk in both the UK biobank (OR, 1.00; 95% CI, 0.94-1.06; FDR, 0.98) and FinnGen studies (OR, 0.96; 95% CI, 0.92-1.02; FDR, 0.68). No strong evidence of an association was found between genetically predicted AD and the risk of any site-specific cancers.Our MR investigation does not support a causal effect of AD on cancer risk. This finding has important implications for the prevention and management of both AD and cancer, as it reduces the concern of potential adverse effects of AD on cancer outcomes.This article is protected by copyright. All rights reserved.