Spherical cavity transducer can generate high acoustic pressure in a narrow focal region at a sub-wavelength level, which suggests a great potential application in high intensity focused ultrasound (HIFU) treatment. In this paper, tissue lesion induced by a spherical cavity transducer is investigated based on the nonlinear acoustics theory and bio-heat transfer theory. A 430 kHz spherical cavity transducer with a diameter of 240 mm is used to generate tissue lesion for liver tissues. The result shows that the tissue lesion with a size less than a wavelength can be formed under the 2 s HIFU exposure at a acoustic pressure of 53 kPa. The numerical simulations coincide well with the experimental measurements, and the optimization of the design of the spherical cavity transducer is also discussed. This work demonstrates that the spherical cavity transducer can be used in the accurate HIFU tumor treatment.