Herein, TiO2/NiCr2O4 nanocomposites with p-n heterojunctions were synthesized via a refluxing method and used with peroxydisulfate (PDS) to produce extensive reactive radicals. Textural, optical, photoelectrochemical, structural, and morphological properties of the prepared materials were extensively investigated. After adding 1.48 mM PDS, the removal rate constant of tetracycline hydrochloride (TH) over the TiO2/NiCr2O4 (20%)/PDS system was almost 20.5, 7.24, and 5.91-times as high as the pristine TiO2, TiO2/PDS, and TiO2/NiCr2O4 (20%) samples, respectively. Therefore, the synergistic effect of PDS and heterogeneous photocatalysis remarkably impacted the degradation reaction of TH. It was proposed that all h+, •O2−, •OH, and SO4•- contributed to the degradation reaction. According to the formation of heterojunction between n-TiO2, and p-NiCr2O4 semiconductors, a plausible mechanism for removal of different contaminants in the TiO2/NiCr2O4/PDS system was discussed. © 2022 Elsevier Ltd