A high intensity focused ultrasound therapeutic system guided by an imaging device is provided and includes an ultrasound therapeutic applicator which contains an ultrasound transducer (8), a therapeutic bed (11), on which a patient (17) lies, and an imaging device used for imaging a diseased tissue (3). Wherein, the imaging device is a non-ultrasound imaging device with two-dimensional imaging function. The ultrasound transducer (8) with the diameter of focal core (23) ranging from 0.1mm to 5mm, preferably, ranging from 0.2mm to 2mm, in a biological focal region (2) located in the diseased tissue (3) is adopted. The non-ultrasound imaging device is a CT or an MRI device with two-dimensional imaging function. The present invention can image the target accurately, so it can be applied to all kinds of complicated surgeries and has good therapeutic effects.