It is of great significance to degrade antibiotics contamination by visible-light photocatalysis, however, exploiting photocatalysts with a strong visible light response, high efficiency, and stability remains a major challenge. Herein, a direct Z-scheme photocatalyst based on ZnIn2S4@MoO3 has been obtained, in which ZnIn2S4 nanosheets in-situ grow on MoO3 nanowire. The optimized composite exhibits good catalytic activity for the visible-light-driven degradation of tetracycline hydrochloride (TC-HCl), of which the reaction rate is 25.8 and 7.8 times that of the pristine MoO3 and ZnIn2S4, respectively. The experiment results and density function theory (DFT) calculation revealed that the improved performance could be attributed to the Z-scheme charge transfer mechanism inside of the heterojunction, which can simultaneously mediate the direction of photoinduced charge migration, boost the charge transfer, and maintain the high redox capacity of photogenerated electrons or holes. Moreover, possible TC-HCl degradation routes are also proposed. This work could further motivate the rational design and synthesis of Z-scheme heterojunction photocatalysts for removing antibiotics from the natural environment via visible light irradiation.