Background and objectives To investigate the efficacy of indocyanine green (ICG) fluorescence-guided laparoscopic hepatectomy for the treatment of secondary malignant liver tumors. Method Data from patients with secondary malignant liver tumors who underwent laparoscopic hepatectomy were retrospectively collected. The patients were divided into a fluorescence group (those who underwent ICG fluorescence-guided hepatectomy) and a conventional group (those who underwent hepatectomy without ICG fluorescence guidance). Surgical time, tumor clearance rate, and postoperative complications were compared between the two groups. Result Laparoscopic hepatectomy was successfully performed in all the enrolled patients. Compared to the conventional group, the fluorescence group experienced shorter surgical time (234.23 ± 74.14 vs. 291.18 ± 104.34 min), less blood loss (123.08 ± 67.75 vs. 197.06 ± 163.43), lower ALT level (420.06 ± 360.69 vs. 254.50 ± 162.29 IU/L) on the 1st or 2nd postoperative days, and wider tumor margin (all P < 0.05). No significant differences were found in the postoperative complication rate (11/26 vs. 9/17), tumor clearance rate (92.31% vs. 88.24%), or postoperative 3-month recurrence rate (2/26 vs. 1/17) between the two groups (all P>0.05). Conclusion ICG fluorescence-guided laparoscopic hepatectomy can shorten the surgical time, reduce intraoperative blood loss, and reduce the incidence of postoperative liver dysfunction in the treatment of secondary malignant liver tumors. It can also improve the tumor clearance rate and is safe and feasible for perioperative implementation.