Developing multicolor upconversion nanoparticles (UCNPs) with the capability of regulating their emission wavelengths in the UV to visible range in response to external stimuli can offer more dynamic platforms for applications in high resolution bio-imaging, multicolor barcoding and driving multiple important photochemical reactions, such as photoswitching. In this communication, we have rationally designed single crystal core-shell structured UCNPs which are capable of orthogonal UV and visible emissions in response to two distinct NIR excitations at 808 and 980 nm. The orthogonal excitation-emission properties of such UCNPs, as well as their ability to utilize low power excitation, which attenuates any local heating from the lasers, endows the UCNPs with great potential for applications in materials and biological settings. As a proof of concept, the use of this UCNP for the efficient regulation of the two-way photoswitching of spiropyran by using dual wavelengths of NIR irradiation has been demonstrated.