A mathematical model for dilution crystallization of spectinomycin dihydrochloride pentahydrate was established on the basis of the population and mass balance. Three operating modes, i. e., constant mass rate addition of diluent, constant mass fraction of diluent and constant size-independent growth rate, were investigated over a wide range of controlled parameters. The intrinsic characteristics of the crystallization process and the influence of operation parameters were analyzed in detail. Suitable strategy for better performance was suggested.