Hydrodynamic cavitation (HC) (typically used to generate submicron bubbles) are frequently examined to improve froth flotation efficiency of ultrafine particles (−38 µm); however, the study of their effects on flotation parameters during the process of coarse particles (+100 µm) was not significantly explored. The main aim of this investigation is to discover the impacts of HC on effective flotation variables and flotation recovery of coarse particles (FRCP). Various surfactants (frothers: Methyl isobutyl carbinol (MIBC) and pine oil (PO), and dodecyl amine (DDA)) were used for the HC conditions. For comparison purposes, two series of flotation experiments in the absence and presence of HC were conducted by using coarse pure quartz particles (−425 + 106 µm). Variable importance measurements (VIMs) of random forest were applied to compare and assess impacts of flotation parameters (particle size, flotation conventional bubble (CB) size, impeller speed, and air flow rate) on FRCP in the absence and presence of HC. Outputs of VIMs indicated that the negative effect of particle size on FRCP was decreased and the capability of CB for floating coarse particles was improved in the presence of HC. Moreover, VIM results showed that in the presence of HC, the highest FRCP can be achieved when turbulent is lower. Generally, variations in the airflow rate had negligible impacts on FRCP. Flotation experiments suggested that HC in the presence of the collector can overcome the absence of frothers in a flotation system. These results can be used for enhancement of selective separation via froth flotation.