Laparoscopic cholecystectomy (LC) is the gold-standard treatment for cholelithiasis and cholecystitis. In difficult cases with severe inflammation and adhesions, the risk of bile duct injury (BDI) is significantly higher. Precise identification of anatomical biliary structures is essential to prevent such injuries. Conventional intraoperative visualization techniques (IVT) have limited clinical application due to their complexity, increased trauma, and high error rates. Near-infrared fluorescence (NIRF) imaging, utilizing indocyanine green (ICG) as a fluorescent dye, has emerged as an innovative IVT technique. It is increasingly recognized as a feasible, safe, and effective approach for LC. However, the efficacy of NIRF in difficult LC procedures remains unclear, and the optimal timing and dosage of ICG administration are yet to be established. This article outlines the main steps for performing fluorescence-guided difficult LC in a patient with acute gangrenous cholecystitis and evaluates the imaging effects of NIRF in various scenarios. The patient was positioned supine, with four trocars placed. Upon switching to fluorescence mode, the fluorescently labeled bile ducts were readily identified. Following fluorescence guidance, Calot's triangle was carefully dissected. The cystic duct (CD) and cystic artery (CA) were individually identified and clipped before the gallbladder was extracted. Finally, the surgical field was inspected in fluorescence mode to detect bile leakage. With satisfactory ICG imaging and a smooth procedure, the patient's postoperative recovery was uneventful. NIRF is a safe and effective technology that shows great promise for future clinical applications.