BACKGROUND: l-cysteine plays an important role in protein synthesis, osmoregulation, detoxification, nervous system function, and antioxidant process. Low levels of cysteine are associated with various diseases like cardiovascular diseases, ischemic stroke, neurological disorders, diabetes, cancer like lung and colorectal cancer, renal dysfunction-linked conditions, and vitiligo. Therefore, it is of great significance to develop a rapid and accurate method for the determination of cysteine concentration. RESULTS: A photoelectrochemical (PEC) biosensor based on PbCrO SIGNIFICANCE: Our PEC sensor has been successfully used for the detection of l-cysteine in human blood serum. This work provides a new inspiration for the great practical application of PEC sensors in medicine and clinical diagnosis fields.