Developing efficient signal enhancement and interference reduction methods is essential for the sensitive determination of disease-related biomarkers. Owing to the complexity of clinical diagnosis and prognostic management of melanoma, there is an urgent need to develop sensitive and accurate assays. Herein, we developed a self-powered photoelectrochemical (SP-PEC) immunosensing device based on an optimized ion adsorption strategy for achieving an ultrasensitive method for the determination of lactate dehydrogenase (LDH). Briefly, In2O3/In2S3 heterojunctions with complex surface structures were synthesized using a multistep modification approach, to generate ultra-high self-powered voltage (0.23 V) and photo-responsive output current (76 mu A cm-1), which was attributed to the efficient internal carrier migration under photoresponsivity of the heterostructure of the developed SP photoanode. Optimized ion adsorption modeling demonstrated that the developed composite photoanode was ultra-sensitively responsive to Hg2+. Sensitive target evaluation was achieved by HgO functionalized detection antibody (HgO-dAb) and immune complex formation in the presence of LDH. The developed sensor provides flexible detection of LDH from 100 to 50 000 pg mL-1 with a detection limit as low as 38.2 pg mL-1. This work provides a new vision for the development of an efficient photoelectrochemical immunosensing system.