Laser ablation has been used in different surgical procedures to perform precise treatments. Compared with previous free-beam laser delivery systems, flexible-optical-fiber-based systems can deliver laser energy to a curved space, avoiding the requirement of a straight working path to the target. However, the fiber tip maintains direct contact with the tissue to prevent laser divergence, resulting in fiber damage, uneven ablation, and tissue carbonization. Here, a liquid lens is used to address the problem of laser defocusing when radiating targets at different depths for flexible-optical-fiber-based systems. The liquid lens focuses a laser with a maximum power of 3 W onto a medium-density fiberboard at a focal length of 40–180 mm. The relationships between the ablation crater diameter and depth with the radiation time and laser power have been quantitatively evaluated through OCT (optical coherence tomography) imaging. Experiments demonstrate that the liquid lens can continuously focus the high-power laser to different depths, with the advantages of compact size, fast response, light weight, and easy operation. This study explores liquid-lens-based focused laser ablation, which can potentially improve the performance of future medical image-guided laser ablation.