Quantitative ultrasound (QUS) is a novel imaging technique that is hypothesized to be capable of monitoring of High Intensity Focused Ultrasound (HIFU) treatment by quantifying tissue changes during exposure. Experiments were conducted on fresh liver samples from rats and lesions were formed using a HIFU system (1-MHz, f/1.2). A wire thermocouple was inserted into the sample to monitor temperature elevation. Backscattered time domain waveforms were recorded using a clinical imaging system (Ultrasonix, L14-5 linear array) during the HIFU application and backscatter coefficients were estimated using a reference phantom technique. Two parameters were estimated from the backscatter coefficient (effective scatterer diameter (ESD) and effective acoustic concentration (EAC)) and two parameters were estimated from the envelope statistics (k parameter and μ parameter) of the backscattered echoes. At the end of the exposure the ESD, EAC and k parameters changed in the treated region by 20%, 50% and 15% respectively, compared to the untreated region. Furthermore, changes in QUS parameters followed the shape of the temperature profile recorded by the thermocouple. These results suggest that QUS techniques could be used for noninvasive thermometry of HIFU.