A novel approach combining dual frequency and split focus approaches is proposed to substantially enhance heating in treatment by using a prototype broadband splitfocus transducer. Using a dual-frequency mode in which the higher frequency is twice the lower frequency, the superimposition of two frequency pressures in the confocal region can enhance nucleation cavitation and inertial cavitation activity. Ex vivo liver or gel phantom experiments using the dual frequencies of 1.2 and 2.4 MHz confirmed a lesion size about two times larger than that obtained using a single 1.6 MHz frequency. The mean square indicating inertial cavitation energy from filtered passive cavitation detection (PCD) data demonstrated that the inertial cavitation activity dominated the enhanced heating rate and that the extra frequency components in the dual-frequency case contributed to increasing the lesion size. The dual-frequency, split-focus protocol takes great advantages of temporally and spatially enhanced-cavitation heating. The results revealed that the dual-frequency, split-focus method enhanced the heating rate one order of magnitude more than other methods. The inertial cavitation energy waveform revealed that the strong inertial cavitation action was involved in enhanced heating in the entire 22 s treatment. The greater spatial area of preformed bubble-layer surface reflection (or scatter ultrasound) regime in the dual-frequency, split-focus protocol enhanced the proximal acoustic field and enlarged the enhanced-pressure field toward the transducer about 3 times in the axial original-focal dimension, as well as laterally. This regime supported the sustained inertial cavitation during a 22 s treatment. An increased pulse-repetition frequency (PRF) protocol was formed using dual frequency and split focus, increasing PRF from 1 to 10, 20, and 40 Hz to take advantage of pulse-induced cavitation. The experiments demonstrated that the lesion size with 20 Hz PRF was about 2.5 times that obtained with 1 Hz PRF, and possessed quick 0.2 s lesioninception time. Within the high-frequency band, the inertialcavitation frequency integral was approximately proportional to the lesion size of 1, 10, 20, and 40 Hz PRF respectively, indicating higher frequency contribution to enhanced heating.