Background: Processed meat and alcohol have been consistently associated with breast cancer risk, but evidence for their effects in women with different genetic susceptibility of breast cancer is scarce, and little is known about their interactions.<br /><br />Methods: We analyzed data from 260,779 female participants in the UK Biobank. Multivariable adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between processed meat and breast cancer risk. We further assessed its interaction with alcohol intake and polygenic risk score (PRS) for breast cancer.<br /><br />Results: Processed meat intake more than once a week was positively associated with risk of breast cancer, especially in women took alcohol ≥1/d (HR=1.50, 95% CI=1.17-1.93), and in women who usually took alcohol together with meals (HR=1.70, 95% CI=1.21-2.39, P for interaction=0.048). The association between processed meat and breast cancer did not differ by menopausal status. When further stratified by PRS, processed meat more than once a week intake was associated with risk of breast cancer (HR=1.17, 95% CI=1.02-1.35) in women with the highest quantile of PRS, and additive interaction was found between them.<br /><br />Conclusion: Processed meat was associated with risk of breast cancer in women, and the effect was stronger in those who took alcohol together with the meal and with high PRS of breast cancer, suggesting the focus of future preventive measures on these women.<br /> Funding: This work was supported by the Natural Science Foundation of Fujian Province [grant no: 2021J01721], the Startup Fund for High-level Talents of Fujian Medical University [grant no: XRCZX2020007], Startup Fund for Scientific Research, Fujian Medical University [grant no: 2019QH1002] and Laboratory Construction Program of Fujian Medical University [grant no: 1100160208].