A novel signal-off biosensing platform based on the CdLa2S4/SnIn4S8/Sb2S3 heterojunction as photoactive materials and NiCo2O4 nanospheres as a photoquencher was developed to achieve the sensitive detection of CA19-9. First, the narrow band gap hydrangea-like CdLa2S4/SnIn4S8/Sb2S3 not only provided excellent photocurrent response but also supplied a mass of active sites that facilitated the loading of capture antibody (Ab1). Second, a double type II CdLa2S4/SnIn4S8/Sb2S3 heterojunction promoted the fast separation and migration of photogenerated e-/h+ and overcame the problem of short carrier lifetime caused by the recombination of photogenerated carriers. In addition, to improve the sensitivity of the constructed sensor to detect CA19-9, signal tags (p-type NiCo2O4) with large steric hindrance were introduced to accomplish signal amplification by the effect of double signal quenching. On one hand, NiCo2O4, which was strongly responsive to visible light, utilized its own advantages to compete for AA with CdLa2S4/SnIn4S8/Sb2S3, resulting in a decrease in the hole scavenging rate of the substrate. On the other hand, the photoquencher NiCo2O4 also prevented AA from contacting the matrix and further aggravated the photoelectrochemical (PEC) signal-damping effect. The PEC immunosensor was prepared with brilliant selectivity and splendid stability to detect CA19-9 (0.001-50 U/mL), and the detection limit was 0.0004 U/mL (S/N = 3).