In recent years, people have been actively exploring new imaging methods with high biological imaging performance because the clinical image definition and depth in vivo cannot meet the requirements of early diagnosis and prognosis. Based on the traditional near-infrared region I (NIR-I), the molecular probe of the near-infrared region II (NIR-II) is further explored and developed. In the NIR-II region due to the wavelength is longer than the NIR-I region can effectively reduce the molecular scattering, optical absorption of the organization, the organization of spontaneous fluorescence negligible, thus the NIR-II Fluorescence imaging (FI) can get deeper penetration depth, higher signal-to-background ratio (SBR) and better spatiotemporal resolution, FI in NIR-II region are an important and rapidly developing research region for future imaging. In the NIR-II fluorophore, small organic molecule fluorophore has attracted much attention because of its good biocompatibility and good pharmacokinetic properties. In this review, we briefly introduced the existing NIR-II organic small molecule fluorophores, and introduced the existing relatively mature methods for improving quantum yield and water solubility, and the small molecule dyes on FI of various improvement methods, also briefly introduces the small molecules of photoacoustic imaging (PAI), and a brief introduction of imaging-guided surgery (IGS) for some small organic molecules, finally, a reasonable prospect is made for the development of small organic molecules. Display omitted