Clinoptilolite-Na, Na2.55Ca1.67K0.37(H2O)21.5[Al6.21Si29.79O72], with the space group C2/m, a = 17.6229(4), b = 17.9957(3), c = 7.39625(15) Å, β = 116.353(3)°, V = 2101.85(7) Å3, and Z = 1 has been studied by single-crystal X-ray diffraction method in normal conditions as well as under compression in penetrating (water-containing) and non-penetrating (paraffin) media. When compressing in water medium, clinoptilolite is subjected to the additional hydration at the starting stage unlike the structurally similar heulandite with persistent increasing the content of H2O over the wide pressure range. This occurs owing to the additional population of partially vacant positions. With further increasing the pressure, H2O molecules are redistributed in the extraframework subsystem saving the total number. Both literature and our data on compression of zeolites of the isomorphous heulandite-clinoptilolite series in non-penetrating media evidence that the compressibility along the coordinate directions noticeably differs from sample to sample including differences in the direction of the largest compression. This is evidently associated with variations in the zeolite composition.