The present paper investigated the potential of hydrodynamic cavitation (HC) as an effective tool for activating sodium percarbonate (SPC). The method's efficiency was demonstrated by effectively removing estrogens, which are pollutants that have adverse impacts on aquatic ecosystems. The effects of the SPC concentration, temperature of solution, and cavitation time were evaluated. After SPC/HC treatment, the removal of estrogens was monitored by liquid chromatography-tandem mass spectrometry (LC -MS/MS). Already after 4 s of treatment and 24 h of reaction time, more than 97% of estrogens (initial concentration of 300 ng/L) were removed. The effect of post-treatment time is not considered in several papers, even though it seems to be crucial and is discussed here. The results were supported by the values of degradation rate constants, which fit the pseudo-first-order kinetic model. We also verified that HC alone was not effective for estrogen removal under the selected conditions. The sustainability of the SPC/HC system was evaluated based on electric energy per order calculation. The combination of SPC and HC is a promising approach for rapidly degrading micropollutants such as estrogenic compounds without the need for additional technological steps, such as pH or temperature adjustment.