Display omitted •3D PANI/PDI organic heterojunction was successfully constructed.•Excellent photocatalytic performance and stability for TC degradation.•Larger delocalized π-conjugated system and energy-matched heterojunction structure.•Possible pathways and mechanism of photocatalytic degradation of TC. Polyaniline/Perylene diimide organic heterojunction photocatalyst with three-dimensional structure (3D PANI/PDI) has been successfully prepared via an in-situ growth process. 3D PANI/PDIexhibited efficient performance in the degradation of tetracycline (TC) under visible light irradiation. The degradation rate of TC by 3D 20%-PANI/PDIis 15.3 times and 17.0 times that of pure PDI and PANI in static system, respectively. Moreover, 3D PDI/PANI showed outstanding stability and could continuously degrade TC for up to 75 h in a dynamic system. The enhanced photocatalytic performance and stability of 3D PANI/PDI mainly comes from the following three aspects: (i) The introduction of PANI polymer backbone reinforced the strength of the PDI hydrogel, thereby improved the catalytic stability of the system; (ii) The three-dimensional network structure provided more reactive sites and medium transport channels; (iii) Larger delocalized π-electron conjugated system and energy-matched heterojunction structure were established through π-π interactions between PANI and PDI, which improved the efficiency of the migration and separation of photo-generated carriers. Finally, the mechanism and mineralization pathways of TC were systematically studied. Superoxide radical (O2−), hydrogen peroxide (H2O2) and hole (h+) were the main reactive species (RSs) for the degradation of TC. Under the attack of RSs, the TC under hydroxylation, dealkylation, aromatization, and ring-opening processes, eventually leading to complete mineralization. This work provides a new promising approach for improving the photocatalytic performance of organic catalysts and indicates that 3D PANI/PDI organic heterojunction photocatalyst can be efficiently applied for the water environmental remediation.