Adsorption and desorption are critical to crystal engineering for the protein crystal applications. In this paper, we present a new method to study the adsorption and desorption kinetics of waters in lysozyme crystals. H2O and D2O were used as ideal indicators for the purpose. The lysozyme crystals were prepared in a complete D2O environment to ensure that all the water molecules in crystal were D2O. The H2O in the gas phase directly exchanges with the D2O in the crystal by exposing the crystal to an ambiance with saturated water vapor. Using in situ confocal Raman microscopy, H2O adsorption and D2O desorption in the lysozyme crystals were found to follow first-order kinetics. The rate constants of H2O adsorption and D2O desorption were obtained to be equal to each other. The kinetic rates were found to linearly depend on the surface area-to-volume ratio of the crystals.