AbstractIntroductionThis study aimed to investigate the effect of fat‐layer thickness and focal depth on the pressure and temperature distribution of tissue.MethodsComputer simulations were performed for the skin–fat layer models during high‐intensity focused ultrasound (HIFU) treatment. The acoustic pressure field was calculated using the nonlinear Westervelt equation and coupled with the Pennes bioheat transfer equation to obtain the temperature distribution. To investigate the effect of the thickness of the fat layer on pressure and thermal distributions, the thickness of the fat layer behind the focal point (z = 13.5 mm) changed from 8 to 24 mm by 2 mm step. The pressure and temperature distribution spectra were extracted.ResultsThe simulated results were validated using the experimental results with a 98% correlation coefficient (p < 0.05). There was a significant difference between the pressure amplitude and temperature distribution for the 8–14 mm thickness of the fat layer (p < 0.05). By changing the focal point from 11.5 to 13.5 mm, the maximum acoustic pressure at the focal point increased 66%, and the maximum temperature was 56%, respectively.ConclusionConsidering the specific treatment plan for each patient, according to the skin and fat layer thicknesses, can help prevent side effects and optimize the treatment process of HIFU.