In the present study, a heterogeneous catalytic hydrolysis system was developed to remove streptomycin and its antibacterial activity from an aqueous solution as well as a streptomycin production wastewater using a solid base catalyst by supporting CaO onto MgO (CaO/MgO). As compared to the traditional catalyst aqueous NaOH under the same aqueous conditions (pH = 10.3 +/- 0.1, 55 degrees C), the half-life (t(1/2)) of streptomycin in aqueous solution containing 20 mg L-1 of streptomycin was shortened from 7.22 h to 1.63 h in the presence of CaO/MgO-0.24. The result of temperature programmed desorption with CO2 (CO2-TPD) showed a strong positive correlation between the strong base sites (low-coordination O2- anions) on the CaO/MgO surface and streptomycin hydrolysis t(1/2) (r(2) = -0.943, p = 0.005). The underlying mechanism for the hydrolytic degradation was proposed using density functional theory (DFT) in combination with ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). The surficial base sites of the catalyst attacked the two ether C-O bonds connected to the ring with the streptose structure of streptomycin, resulting in the formation of four hydrolysis products with far less antibacterial activity. The optimized CaO/MgO catalyst was used for the removal of streptomycin from the production wastewater containing 2218 mg L-1 of the target antibiotic and 10 178 mg L-1 of chemical oxygen demand (CODCr). It was found that 98% of streptomycin as well as its antibacterial activity was removed within 2 h with a catalyst dose of 15.0 g L-1. The CaO/MgO solid base catalyst exhibited a good application prospect in the pretreatment of antibiotic production wastewater.