Surface acid site regulation of photocatalysts is a promising strategy to improve their performance. Herein, surface acid sites of cadmium sulfide were rationally regulated by cerium doping, which resulted in significantly increased photocatalytic activity for tetracycline hydrochloride (TC-HCl) degradation. The generated Brønsted acid sites were verified to favor the adsorption of organic molecules because of their strong affinity. Meanwhile, Lewis acid sites acted as the active sites for C-C bond cleavage via a nucleophilic substitution process, which was testified by the Fukui function and electrostatic potential. Besides, Ce3+ doping suppressed the recombination of electron-hole pairs, which also boosted the performance of TC-HCl degradation. Moreover, the degradation pathway of TC-HCl was deduced based on theoretical calculations and HPLC-MS results. The toxicity of pollutants and intermediates was also evaluated. This work provided new insight into the rational design and preparation of highly efficient photocatalysts for environmental purification.