<p>We propose a robot-assisted method to generate spherical thermal lesions by high-intensity focused ultrasound (HIFU) ablation. Typically, HIFU-induced thermal lesions are cigar-shaped because the acoustic field in the focal area has a similar elongated shape. We assumed that HIFU irradiation with a certain range and pattern of motion could influence the heat transfer within the target area, allowing control over the lesion’s shape and size. Based on the simulations of various motion models likely to induce a change of heat transfer pattern around the target area, we identified Gaussian random motion (GRM) as the optimal motion model for generating spherical thermal lesions. In the experiment, the GRM model was tested using a robotic arm on bovine serum albumin (BSA) gels. The transparency of the BSA gels allowed us to record the temporal changes in thermal lesions and compare them with those produced by conventional fixed-focus HIFU ablation. The experimental results showed that the average sphericity of the thermal lesions generated by the GRM model was 0.85, indicating that this method can produce nearly spherical lesions. In contrast, fixed-focus HIFU ablation resulted in elongated lesions with a sphericity of 0.33. As a result, focal motion using the GRM model enables HIFU ablation to generate spherical thermal lesions. We expect this approach to be applicable for non-invasive HIFU treatments of small, spherical tumors that can be detected at an early stage.</p>