Abstract Background: Obesity, the modern ‘epidemic’, has shared correlation with fatty liver disease and breast cancer. However, previous studies on the relation between fatty liver and breast cancer have shown conflicting results on the impact of fatty liver on the survival and recurrence of breast cancer patients. And there was no attempt to find out the effect of liver fibrosis, which is the consequence of fatty liver disease, on female breast cancer patients. So we attempted to investigate the prognostic value of non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis(NASH)-related liver fibrosis in patients with breast cancer undergoing surgery, using noninvasive tools like liver-to-spleen attenuation(L/S) ratio and Fibrosis-4(FIB-4) score, respectively. Methods: A total of 933 patients diagnosed with primary invasive breast cancer and receiving surgery at the university-affiliated referral center between April 2006 and December 2019 were included. After excluding patients who had significant alcohol consumption and hepatitis viral infection,838 patients were divided into two groups according to the L/S ratio of 1 measured by the preoperative low-dose computed tomography: 91 patients(10.9%) with a L/S ratio< 1 vs 747 patients(89.1%) with a L/S ratio≥1. They were also divided into two groups based on the FIB-4 score of 2.67: 804 patients (95.9%) with a FIB-4 score< 2.67 vs 34 patients (4.1%) with a FIB-4 score≥2.67. The Cox proportional hazards model was used to calculate the hazard ratio (HR) and the 95% confidence interval (CI). Results: Patients with NAFLD were older, had higher BMI, and had a higher proportion of mastectomy and hyper-transaminasemia. They showed worse overall, disease-free, and regional recurrence-free survivals compared to those without NAFLD (p=0.008, 0.043, and 0.017, respectively), but no significant differences in local recurrence-free, systemic recurrence-free, and contralateral breast cancer-free survivals. The survival outcome of breast cancer did not show any relationship with NASH-related liver fibrosis (overall survival; p=0.061, disease-free survival; p=0.557). NAFLD was a significant risk factor for mortality in multivariable analysis (HR, 2.077; 95% CI, 1.052–4.102; p=0.035). After stratifying for subtypes of breast cancer, the L/S ratio remained a significant predictor of overall, disease-free, local recurrence-free, and regional recurrence-free survivals in only the hormone receptor-positive/HER2−negative subtype (p=0.007, 0.005, 0.009, and < 0.001, respectively). Conclusion: NAFLD is significantly associated with decreased overall survival, disease-free survival and increased regional recurrence in patients with breast cancer especially the hormone receptor-positive/HER2−negative subtype. NASH-related fibrosis was not associated with survival. Therefore, NAFLD should be assessed in the preoperative setting for predicting long-term prognoses of breast cancer patients Citation Format: Hyunsu Yeoh, Siwon Jang, Jong-Ho Cheun, Jin Ah Kwon, Myoung Seok Lee, Bumjo Oh, In Sil Choi, Sohee Oh, Jongjin Kim, Jeong Hwan Park, Won Kim, Ki-Tae Hwang. Prognostic impact of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis-related liver fibrosis on postoperative long-term outcomes of breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-06.