Hepatectomy is a main therapeutic strategy for hepatocellular carcinoma (HCC), which requires removal of primary and disseminated tumors and maximum preservation of normal liver tissue. However, in a clinical operation, it is difficult to recognize the tumor tissue and its boundary with the naked eye and palpation, which often leads to insufficient or excessive resection. Near-infrared fluorescence (NIRF) imaging, a non-invasive, real-time, low-cost, and highly sensitive imaging technique has been extensively studied in surgical navigation. With the development of fluorescence imaging system and fluorescent probe, intraoperative tumor detection and margin definition can be achieved, making the operation more accurate.Advances in fluorescence imaging of HCC in the NIR region have focused on the traditional first NIR window (NIR-I, 700-900 nm), and have recently been extended to the second NIR window (NIR-II, 1,000-1,700 nm). Compared with NIR-I imaging, fluorescence imaging in the NIR-II exhibits great advantages, including higher spatial resolution, deeper penetration depth, and lower optical absorption and scattering from biological substrates with minimal tissue autofluorescence. There is no doubt that developing novel NIRF probes for in vivo imaging of HCC has high significance and direct impact on the field of liver surgery.In this article, the development of various NIRF probes for fluorescence image guided HCC hepatectomy is reviewed, and current challenges and potential opportunities of these imaging probes are discussed.