High-powered lasers are commonly used for tissue resection in surgeries, including liver resection, medically known as hepatectomy; however, such lasers inevitably induce thermal damage that causes postoperative complications. This study aims to explore the effects of water cooling and different laser output modes on laser-induced thermal damage during hepatectomy. Methods: To avoid the influence of superposition, a 980-nm diode laser was used for a single-point hepatectomy. Eighteen Sprague-Dawley rats were used to explore the effects of water cooling and different laser output modes. A constant energy 10-J laser was used to cut the liver tissue with a power of 10 W and time of 1 second. The rats were randomly divided into six groups. The first three groups were assigned as test subjects for different laser output modes. Group 1 was operated with a continuous laser output for a duration of 1 second. Groups 2 and 3 were operated with a pulsed laser output for a duration of 1 second and a pulse width of 0.5 and 0.25 seconds, respectively. Groups 4, 5, and 6 were assigned for the water cooling test. Water cooling was performed based on the parameters of the first three groups. Medical saline (0.9% NaCl) was used for water cooling. The main observation indicators were resection efficiency and thermal damage, including the area of the thermal damage zone. Resection efficiency is calculated by dividing the resection area by the total thermal damage area. Results: In the three water cooling groups, the area of the resection, carbonized, sub-boiling coagulated, and total thermal damage zones were 0.0677, 0.00, 1.7293, and 2.2982 mm 2 in Group 4; 0.0465, 0.00, 1.3205, and 1.8414 mm 2 in Group 5; and 0.0565, 0.00, 1.4301, and 1.9650 mm 2 in Group 6, respectively. Compared with the first three groups, the water cooling groups exhibited significantly reduced thermal damage areas of in the carbonized, sub-boiling coagulated, and total thermal damage zones (p < 0.001 for all). In addition, there was no statistical difference in the resection area, vacuolated area, and resection efficiency. Furthermore, there was no statistical difference in the area of each thermal damage zone between the continuous and pulsed output groups. The resection efficiencies were 4.82%, 3.34%, 3.73%, 3.93%, 3.36%, and 3.01% in Groups 1 to 6, respectively. Moreover, there was no statistical difference (p > 0.05) in the resection efficiencies. Conclusion: Water cooling can reduce the total laser-induced thermal damage area and prevent tissue carbonization. Therefore, this cooling method can be used as a simple and safe strategy for controlling thermal damage during hepatectomy.