In the present study, ZnO nanostructures were ultrasonically synthesized and immobilized on the surface of diatomite and used for visible light photocatalysis of Acid Red 88 (AR88) in the aqueous phase. Scanning electron microscopy (SEM) and X-ray diffraction (XRD) analyses were employed for characterization of the samples. The process was optimized via response surface methodology (RSM) on the basis of central composite design (CCD). Based on numerical optimization, for the maximized color removal of 96% the initial dye concentration, the catalyst dosage, the reaction time, and the initial pH were 13 mg/L, 1.5 g/L, 85 min, and 4, respectively. The initial pH produced the largest effect, while the adsorbent dosage represented the lowest individual effect on the photocatalysis of AR88. The reusability test showed a 20% reduction in decolorization efficiency (%) within four consecutive experimental runs. Overall, ZnO-diatomite nanocomposite can be applied as an efficient photocatalyst for the visible light photocatalysis of target organic dyes.