Due to the strong tissue absorption of short-wave-length light below 600 nm, in vivo imaging based on UCNPs as luminescent probes is still limited. The NIR spectral range (700–1100 nm) and the red region (600–700 nm) are referred to as the “optical window” of the biological tissues because the light scattering, absorbance and autofluorescence of tissue are minimum in this range. Here we synthesized NaYF4:Yb3+,Tm3+/CdS nanoheterostructures. In the nanoheterostructures, the red (700 nm) and NIR (802 nm) emissions of NaYF4:Yb,Tm were enhanced by 7.3 times, while the blue emission peak at 476 nm nearly disappeared and no peak of CdS appeared. Transmission electron microscopy (TEM) images show that the morphology of the binary nanoparticles is predominantly peanut-like and the X-ray diffraction (XRD) patterns of the NaYF4:Yb3+,Tm3+/CdS nanoheterostructure were assignable to both wurtzite phase CdS and hexagonal phase NaYF4:Yb3+,Tm3+. In comparison, introducing Cd2+ ions or S2− ions or preparation of physical mixture of NaYF4:Yb3+,Tm3+ and CdS did not enhance the red (700 nm) and NIR (802 nm) emissions of NaYF4:Yb, Tm. These results indicated that the interactions in the NaYF4:Yb3+,Tm3+/CdS nanoheterostructure played a key role for enhancing the NIR emission of NaYF4:Yb3+,Tm3+ nanocrystals. QDs act as a sub energy level to mediate energy transfer of Tm3+. To evaluate the effect of other QDs on the upconverted fluorescence spectrum of NaYF4:Yb3+,Tm3+, NaYF4:Yb3+,Tm3+/CdSe nanoheterostructures were also prepared by a similar method. The upconverted fluorescence spectra indicated that by conjugation with CdSe, the NIR emission at 802 nm of NaYF4:Yb3+,Tm3+ was also enhanced greatly.