We demonstrate a facile and general strategy based on ligand protection for the synthesis of unstable colloidal nanocrystals by using the synthesis of pure p-type NiO nanocrystals as an example. We find that the introduction of lithium stearate, which is stable in the reaction system and capable of binding to the surface of NiO oxide nanocrystals, can effectively suppress the reactivity of NiO nanocrystals and thus prevent their in situ reduction into Ni. The resulting p-type NiO nanocrystals, a highly demanded hole-transporting and electron-blocking material, are applied to the fabrication of organic solar cells and polymer light-emitting diodes, demonstrating their great potential as an interfacial layer for low-cost and large-area, solution-processed optoelectronic devices.