The Guangzhou Breast Cancer Study (GBCS) is a patient-based prospective cohort study designed to identify risk factors and underlying mechanisms for breast cancer (BC) incidence and prognosis, specifically addressing the need for individualized prevention in South China, where BC incidence is notably high. Based in Guangzhou, China, the GBCS began recruitment in 2008, comprises three complementary studies: the Guangzhou breast cancer cohort with 5471 breast cancer patients, a case–control study with 1551 cases and 1605 controls, and an immunohistochemistry (IHC) cohort with 1063 breast cancer patients. Participants are primarily aged 41–60 years. Cohort follow-up is conducted every three months in the first year, every six months in the second and third years, and annually thereafter. High follow-up rates have been achieved until 2023, with 73.5% for the Guangzhou breast cancer cohort and 98.6% for the IHC cohort still active. Baseline data collection included demographic characteristics and breast cancer risk factors, while follow-up data included survival, treatment details, disease history, occupational history, post-diagnostic lifestyle, and laboratory measures, including genetic markers, proteins, and environmental exposures. The study encourages global collaborations and invites interested researchers to contact the corresponding author at xulin27@ mail.sysu.edu.cn with specific research ideas or proposals.