Breast cancer susceptibility protein-1 (BRCA-1) is a gene directly associated with hereditary breast cancer. BRCA-1 suppresses tumorigenesis, which is crucially involved in cell replication regulation and DNA damage repair, coupled by maintaining normal cell growth. Its accurate and straightforward analysis is essential for clinical diagnosis and treatment. In this study, we fabricated photoactive Z-schemed MoS 2 /CdIn 2 S 4 heterojunctions via hydrothermal synthesis and comprehensively characterized their optical properties using various techniques, with a focus on understanding the interfacial charge transfer process. At the same time, FePdMnCoPt high-entropy alloy/N-doped carbon spheres (termed FePdMnCoPt HEA/NCS) were prepared by confined adsorption and pyrolysis, and their ability to mimic peroxidase (POD)-like acitvity was investigated by oxidation of 3,3′5,5′-tetramethylbenzidine (TMB) in the presence of H 2 O 2 . On such basis, a MoS 2 /CdIn 2 S 4 -based photoelectrochemical (PEC) sensor was established for the analysis of BRCA-1. The detection signal was greatly amplified by the catalytic precipitation reaction for 4-chloro-1-naphthol (4-CN) oxidation, as assisted by the FePdMnCoPt HEA/NCS nanozyme. The developed PEC sensor had a broad detection range of (0.1−1.0) × 10 5 pg mL −1 with a lower detection limit of 1.00 pg mL −1 . This study has developed a ultrasensitive PEC biosensor for the quantitative detection of BRCA-1, which holds great promise for clinical diagnosis.