Different cation resins, IR-120 and HZ-001, were used as catalysts to prepare validoxylamine A through validamycin A degradation. Herein, influences of reaction time, reaction temperature, resin usage, initial validamycin A concentration, as well as external and internal diffusion limitation, on the degradation ratio of validamycin A were studied. Results demonstrated that validamycin A could almost completely be degraded into validoxylamine A under optimized operation conditions of 5.0% (w/v) resin usage, 1.0%(w/v) initial validamycin A concentration, agitation speed of 200 rpm, and heating at 100℃ for 5h.