Photothermal therapy (PTT) has been widely used for the treatment of various medical conditions due to their noninvasive and cost-effective advantages. However, the light absorption and scattering of the biosystem limit the deep tissue applications of conventional PTT probes. In this paper, we proposed the sub-10 nm NaNdF 4 nanocrystals with both incident and emission wavelengths located at the optical window. Under 800 nm laser excitation, the maximum light-to-heat conversion efficiency of these ultrasmall photothermal agents is evaluated to be 85%. In addition, the conversion efficiency can be further adjusted through varying the doping concentration, changing the probe size, and coating the inert shell. Meanwhile, temperature feedback on the basis of the Nd 3+ luminescence signal validates the precise temperature manipulating inside the biological tissue, evidencing the feasibility of the proposed probes for PTT treatment. Beneficial from the efficient photothermal conversion and low energy loss of excitation/ emission photons in organic tissue, the effective treatment depth of the nanoprobes goes to 6 mm with the actual laser power density only ∼0.2 W/cm 2 . Finally, based on the rapid heating response of the formed nanoprobes, fast ablation treatment of a 1.5 cm pork tissue is achieved using pulsed laser.