Studies on hydrocyclones have evolved over recent years and various configurations of this device have been proposed in the literature for different purposes. Herein, an innovative geometrical configuration of hydrocyclones was developed by means of the response surface technique, combined with an optimization algorithm and supported by a computational fluid dynamics complementary study. The results obtained with these optimization techniques were validated by experimental data. The optimized hydrocyclone configuration is characterized by low energy consumption, i.e., low Euler number, with a small underflow-to-through-put ratio and can be used as a thickener hydrocyclone.