The control of size and size distribution of semiconducting materials has easily carried out by intercalating in clay minerals with tailoring optical properties and activities. The solid-liquid reaction was applied to fabricate zinc selenide nanoparticles in montmorillonite and saponite containing the interlayer expanders of cetyltrimethylammonium cation and 18-crown-6. Various experimental results including XRD pattern, TG-DTA curve, TEM image and the spectroscopic observations of the products could confirm the formation of zinc selenide nanoparticles in smectites in the presence of cetyltrimethylammonium and the absence of 18-crown-6. The pre-expansion of the interlayer nanospace of smectites with cetyltrimethylammonium and 18-crown-6 promoted the facile intercalation of zinc selenide with controlling their particle size. The size of zinc selenide nanoparticles in cetyltrimethylammonium modified smectites was slightly larger than that in pristine smectites. The evident reason on the higher photoluminescence intensity of zinc selenide in cetyltrimethylammonium modified smectites rather than those of zinc selenide in smectite and bare zinc selenide was due to the host-guest and guest-guest interactions. This preparation procedure may be a facile pathway for controlling the particle size and tailoring the optical performance of the unstable semiconductors.