A novel technology was proposed to make a multi-wavelength laser from dye-doped cholesteric liquid crystal (CLC) cell by incorporating the self-assembled polyhedral oligomeric silsesquioxane (POSS) nanoparticles. Due to the multi-domain CLC structure can be realized by the aggregation of the POSS nanoparticles in the CLC cell, multi-wavelength lasing is easily achieved by controlling the self-organization process of POSS/CLC mixture. Since the multi-domain structure of CLC layers can be controlled by POSS-doped concentration and cooling rate, the multi-wavelength lasing performance is easily tuned by the fabrication conditions.