Hydrodynamic cavitation (HC) is a process of vaporization, bubble generation followed by bubble collapse in a flowing liquid brought about by a decrease in pressure followed by a subsequent increase in pressure. We are currently applying this technology in the processing of milk and milk products. Therefore, the objective of this preliminary study was to investigate the effect of hydrodynamic cavitation (HC) on some important properties of milk such as particle size of casein micelles, interactions of proteins and heat stability of skim milk (SM). Pasteurized skim milk (3.5% protein and 9% total solids) was preheated to 50°C and then subjected to 2 sets of HC treatments, namely, HC at 20, 40, and 60 Hz at sufficiently high flow rate (950 L/h) to avoid any temperature increase during HC (T1) and HC at 60 Hz at low flow rates (200 L/h) to allow scale-free heating of skim milk increasing its temperature up to 90°C (T2) using APV Cavitator (supplied by SPX, Denmark) fitted with 4-row rotor in 6mm housing.The samples obtained from T1, T2 and untreated (control) skim milk samples were analyzed for changes in the particle size of casein micelles using Malvern Zetasizer Nano ZS and heat stability using the heat coagulation time (HCT) test at 140°C. The protein interactions in the whole sample and serum phase obtained from these samples were also studied using SDS-PAGE. SM subjected to T1 and T2 did not cause significant changes (P < 0.05) to the casein micelle size and HCT (165–171 nm and >5 min) compared with that in control sample (168 nm and >5 min respectively). On the other hand, samples subjected to T2 exhibited significantly higher levels (P < 0.05) of whey protein denaturation (P < 0.05) compared with those subjected to T1, which was attributed to the heat generated due to cavitation during T2. The high molecular weight aggregates were also generated in samples subjected to T2 due to extensive denaturation of whey proteins and their interactions with casein micelles. The results of this study suggested that HC can be promising technique that can be potentially used as an alternative technology for scale-free heating of milk with minimal effect on important properties of milk.