AbstractThe O‐deficient modified CuAl2O4/MoS2 composite photocatalysts (ODMCAOMSCP) are fabricated by a wet chemical route and low‐temperature treatment for the degradation of tetracycline hydrochloride (TC). The fine particles dotted on the large sheet are revealed to be comprised of large sheets with rich oxygen defects and nanoparticles, which endows it with a high optical absorption coefficient, available reactive species, excellent charge carrier separation, and high photocatalytic activity. The finely designed ODMCAOMSCP achieve a TC degradation first‐order rate constant of 0.01436 min−1, which is 3.99 and 2.70 times higher than that of MoS2 and CuAl2O4, respectively. Response surface analysis reveals that multiple environmental factors including initial TC concentration, catalyst content, and initial pH affect the photocatalytic activity of the catalyst on the basis of backpropagation (BP) neural network optimized by genetic algorithm and Box‐Behnken design. The degradation intermediates and degradation pathways are determined by a liquid chromatograph‐mass spectrometer (LC‐MS). The toxicity of TC over ‐ ODMCAOMSCP is studied by the toxicity analysis software and the cultivation of mung bean. Mechanism investigation demonstrates that the major active species of ODMCAOMSCP for the degradation TC are attributed to oxygen vacancy, hydroxyl radical (∙OH), and superoxide radical (∙O2−).