The two-dimensional molybdenum disulfide (MoS2) nanosheet has been extensively studied as a novel photothermal transducing agent. However, top-down exfoliation to produce MoS2 nanosheets is inefficient, and MoS2 nanosheet surface modification procedures are complex. Here, we report the synchronous synthesis and surface modification of 2D MoS2 nanosheets with a polyvinylpyrrolidone (PVP)assisted one-pot hydrothermal method. Due to the chelating-coordinating effect between the lone-pair electrons of the PVP carbonyl oxygen and the unoccupied 4d orbitals of molybdenum, the PVP chains could graft onto the surface of MoS2 and guide the growth of the nanosheets. The resultant MoS2-PVP nanosheets were ultrasmall (21.4 +/- 4.4 nm) and exhibited excellent colloidal stability. Moreover, the strong near-infrared absorption of the MoS2-PVP nanosheets enabled sensitive photothermal conversion performance (with a mass extinction coefficient of 23.33 L g(-1) cm(-1)) and in vitro/in vivo photoacoustic imaging. The MoS2-PVP nanosheets had excellent in vitro and in vivo compatibility and were used for highly efficient tumor photothermal therapy in xenograft tumor-bearing mice. The findings in this report will facilitate the rational design of stable colloidal 2D transition-metal dichalcogenides for effective photothermal cancer therapy.