Recent years have witnessed a cornucopia toward the construction of transition metal chalcogenides (TMS)-based heterostructured photocatalysts in terms of their fabulous light absorption and suitable energy level alignment. Nevertheless, controllable modulation of photoinduced charge separation/transfer toward target active sites for photoredox catalysis still constitutes an enduringly challenging issue. Herein, tailor-made negatively charged mercaptoacetic acid (MAA)-capped CdX@MAA (X=Se, Te, S) quantum dots (QDs) and positively charged ultra-thin branched poly-ethyleneimine (BPEI) layer building blocks were alternately assembled on the hierarchically ordered TiO2 nanotube arrays (NP-TNTAs) framework for general electrostatic layer-by-layer (LbL) assembly of spatially multilayered NP-TNTAs/(BPEI/CdX QDs)n (X=Se, Te, S) photoanodes. The ultra-thin BPEI polymer layer integrated in-between the interface of CdX QDs functions as cascade hole transfer channel for efficiently extracting the holes photoexcited over neighboring CdX QDs layer and simultaneously, alternately deposited CdX QDs layer serves as pronounced photosensitizer for constructing directional electron flow channel. The unique integration mode and intimate interfacial interaction endowed by LbL assembly render the well-defined NP-TNTAs/(BPEI/CdX QDs)n multilayered heterostructures high-efficiency photoanode toward photoelectrochemical (PEC) water splitting under both simulated solar and visible light irradiation, conspicuously outperforming the single and binary counterparts on account of in-situ generation of two spatially separated charge transfer channels, ultimately synergistically boosting the separation efficiency and prolonging the lifetime of charge carriers. Our work would open up new frontier for strategically mediating the interfacial charge transfer and advancing rational construction of heterostructured photocatalysts for solar energy conversion.