Abstract: Objective To assess the quality of the literature related to the carcinogenicity of perfluorooctane sulfonic acid (PFOS) by using the weight of evidence method, and to reveal its carcinogenic risk through the dose-response relationship. Methods A systematic search was conducted for relevant literature on human epidemiologic studies related to PFOS and cancer up to June 2024, after evaluation and secondary screening based on the guidelines for evaluating the relevance and reliability of toxicological data developed by the China National Center for Food Safety Risk Assessment, the dose-response for breast cancer risk analysis was performed using the cancer slope factor (CSF) method in conjunction with the results of meta-analyses of population-based epidemiological studies. Results From the 2532 retrieved human epidemiological articles, 35 valid articles were screened, of which 22 were high-quality evidence and 13 were of moderate quality in terms of the reliability. 32 articles were graded as “A/B” or “B” in terms of the relevance. Meta-analysis showed that both low serum PFOS levels (<4.77 ng/mL; OR=1.46, 95% CI: 1.18-1.80) and moderate serum PFOS levels (>4.77 ng/mL and ≤15.67 ng/mL; OR=1.07, 95% CI: 1.04-1.10) were positively associated with the risk of breast cancer. The CSF results indicated that for every 1 ng/kg BW/d increment in external PFOS exposure, the attributable risk of breast cancer incidence increased by 1.64×10?3. Conclusion Evidence from a weight-of-evidence evaluation integrated with meta-analysis confirmed a significant dose-response association between PFOS exposure and population-level breast cancer incidence, suggesting that PFOS exposure may be associated with an increased risk of breast cancer.