ZrO2-pumice and ZrO2-tuff nanocomposites were synthesized via a modified sol-gel method and used as efficient catalysts for sonocatalytic degradation of rifampin (RIF). The physico-chemical properties of the prepared catalysts were examined using XRF, SEM, EDX, FT-IR and BET analyses and compared to pure pumice and tuff samples. Subsequently, the efficacy of catalysts in degradation of RIF was assessed under various experimental conditions. Both ZrO2-pumice and ZrO2-tuff (1.5 g L-1) exhibited promising catalytic activity for sonocatalytic degradation of RIF at its initial concentration of 20 mg L-1, natural pH and under ultrasonic irradiation power of 300 W. In this condition, about 95% and 83% of RIF was removed through US/ZrO2-pumice and US/ZrO2-tuff processes, respectively. Furthermore, the influence of the addition of a number of scavengers, enhancers and gases on the degradation of RIF was studied. The pronounced degradation effectiveness of the catalysts under ultrasound irradiation could be assigned to their synergetic ability to produce reactive species and subsequent radical reactions. The intermediate products formed in the solution from degradation of RIF were also identified and a decomposition pathway was proposed using GC-MS, COD, TOC and IC analyses.