We used a Mendelian randomization (MR) method in our research to examine the relationship between genetically determined oily fish intake and breast cancer (BC) incidence.The summary data pertaining to the oily fish intake were acquired from the UK Biobank, which consisted of a sample size of 460,443 people. Information on BC was received from the Breast Cancer Association Consortium (BCAC). We analyzed the causal connection between oily fish intake and BC incidence using various methods, including inverse variance weighting (IVW). Heterogeneity was investigated using Cochran's Q test. IVW, MR-Egger, and MR-PRESSO methods were used for sensitivity analysis. In addition, a multivariate MR adjusted for body mass index (BMI) and weight was used for further research.Two-sample MR results showed that oily fish intake was negatively associated with total breast cancer (odds ratio (OR) 0.58, 95% confidence interval (CI) 0.39-0.87, IVW method), estrogen receptor-positive (ER +) breast cancer (OR 0.44, 95% CI 0.21-0.93, IVW method), and estrogen receptor-negative (ER-) breast cancer (OR 0.53, 95% CI 0.30-0.93, IVW method). The sensitivity analysis did not observe the presence of heterogeneity and horizontal pleiotropy. In multivariate MR analysis, the negative association between oily fish intake and total breast cancer (P = 0.03) and ER- breast cancer (P = 0.04) risk persisted after adjusting for BMI and body weight. However, no correlation was found in ER + breast cancer (P = 0.30).The oily fish intake has a negatively correlated with the incidence of total breast cancer, particularly in the cases of ER- breast cancer. There is a lack of substantial evidence supporting a link between the oily fish intake and the incidence of ER + breast cancer.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.