ZnO/PANi composite was prepared by hydrothermal synthesis of ZnO followed by in situ oxidative polymerization of aniline on the ZnO phase. The morphology, elemental composition, crystal structure, functional groups, and optical properties of the material were characterized by SEM, EDX, XRD, FTIR, and UV-Vis spectroscopy, respectively. The simultaneous effects of solution pH, initial CR concentration, ZnO/PANi catalyst dosage, and the aniline/ZnO mass ratio were investigated using response surface methodology with a four-factor, five-level central composite design comprising 30 experimental runs. Photocatalytic activity was evaluated through the degradation of Congo red under light irradiation. The results showed that wurtzite ZnO was incorporated into the PANi matrix and that the composite exhibited an apparent optical band gap of approximately 2.7 eV. The quadratic model was highly statistically significant (F = 63.34; p < 0.0001), with R2 = 0.983, adjusted R2 = 0.968, predicted R2 = 0.917, and a statistically nonsignificant lack of fit (p = 0.1761). The optimal conditions were identified as pH 3.2, a CR concentration of 74.2 mg/L, a ZnO/PANi dosage of 0.84 g/L, and an aniline/ZnO mass ratio of 18.1 wt.%, yielding an average degradation efficiency of 97.3%. The composite retained its ability to degrade Congo red after four cycles. These findings demonstrate the potential of ZnO/PANi for the treatment of water containing azo dyes.