Exploiting innovative sensing mechanisms and their rational implementation for selective and sensitive detection has recently become one of the mainstream research directions of photoelectrochemical (PEC) bioanalysis. In contrast to existing conventional strategies, this study presents a new liposomemediated method via in situ combining ZnInS nanosheets (ZIS NSs) with SnS 2 to form a ZIS NSs/SnS 2 type-I heterojunction on fluorine-doped tin oxide (FTO) electrodes for highly sensitive PEC immunoassays. Specifically, alkaline phosphatase (ALP)-encapsulated liposomes were confined within 96-well plates by sandwich immunorecognition and subsequently subjected to lysis treatment. Enzymatically produced H 2 S by the released ALP was then directed to react with Sn(IV) to engender the ZIS NSs/SnS 2 type-I heterojunction on the FTO/ZIS NSs-Sn(IV) electrode, resulting in a change in the photogenerated electron−hole transfer path of the photoelectrode and reduction in current signaling. Exemplified by heart-type fatty acid binding protein (h-FABP) as a target, the constructed PEC sensor showed good stability and selectivity in a biosensing system. Under optimal conditions, the as-prepared sensing platform displayed high sensitivity for h-FABP with a dynamic linear response range of 0.1−1000 pg/mL and a lower detection limit of 55 fg/mL. This research presents the liposome-mediated PEC immunoassay based on in situ type-I heterojunction establishment, providing a new protocol for analyzing various targets of interest.