The use of in vivo near-infrared fluorescence (NIRF) imaging techniques for sensitive cancer early detection is highly desirable, because biological tissues show very low absorption and autofluorescence in the NIR spectrum window. Cancer NIRF molecular imaging relies greatly on stable, highly specific and sensitive molecular probes. Nanoparticle-based NIRF probes have overcome some of the limitations of the conventional NIRF organic dyes, such as poor hydrophilicity and photostability, low quantum yield, insufficient stability in biological system, low detection sensitivity, etc. Therefore, a lot of efforts have been made to actively develop novel NIRF nanoparticles for in vivo cancer molecular imaging. The main focus of this article is to provide a brief overview of the synthesis, surface modification, and in vivo cancer imaging applications of nanoparticle-based NIRF probes, including dye-containing nanoparticles, NIRF quantum dots, and upconversion nanoparticles.