Purpose: The purpose of this study is to apply photoacoustic imaging (PAI) to monitor high intensity focused ultrasound (HIFU) process in real-time for accurate evaluation of thermal ablation outcomes.Methods: A photoacoustic (PA) imaging system was used to monitor HIFU ablation process in this study. Single-element, spherically focused ultrasonic transducers with center frequencies of 5 and 10 MHz were used to generate HIFU lesions and detect PA signals in beef kidney during HIFU treatments, respectively. A 25-μm diameter, T-type thermocouple was used to measure the temperature rise during the treatment as well. Thermal dose, which was used to indicate the coagulation of soft tissue, was calculated with the temperature measured by the thermocouple. Detected PA signals were then related to the coagulation of soft tissue through thermal dose calculations. In addition, PA signals from beef kidney coagulating under a constant temperature was obtained to show the changes of PA signals under a constant temperature during soft tissue coagulation.Results: PA amplitude increases during the HIFU process and tends to have a saturation stage after the soft tissue is completely coagulated, which is indicated by a 240 or more TD43 minutes. Also, a linear relation between the PA signal amplitude changes and temperature was observed when monitoring the sole effect of temperature. In addition, PA amplitude changes finally reached a constant value during soft tissue coagulation under a constant temperature.Conclusions: Through measurement of the photoacoustic signal, the authors demonstrated that monitoring thermal dose may be a more appropriate method in HIFU treatment than monitoring temperature.