The structure of hydrocyclone was designed with a series of modifications, and the comprehensive effects of the structural modifications on operation performance indices of hydrocyclones were investigated experimentally with orthogonal design method. Based on the conventional hydrocyclone, the structural modifications with central insertions named winged core, solid core and inner diffuser could increase all the reduced separation efficiency, separation sharpness, cut size, capacity and flow split, and decrease the energy loss coefficient. The structural modification of 20 degrees cone with spiral has the same function. The parabola type of cone part could increase the separation efficiency, separation sharpness, cut size and capacity, and decrease the energy loss coefficient and flow split. For increasing separation efficiency and reducing energy loss coefficient only, straight vortex finder with siphon and straight underflow pipe with cone are efficient structure designs. From experimental results of this study, useful clues or guidance could be obtained for the structure design of hydrocyclones with different target indices in different applications.