Hydrogeochemistry investigations have been carried out in the Pergusa Basin, located in central Sicily (Italy), where Pergusa Lake represents a rare example of natural endorheic lake. In the area, agriculture and tourism are the main anthropic activities and, for this reason, groundwater is exploited for agricultural and domestic purposes. Samplings of lake water and groundwater have been carried out with the aim of characterizing the main physicochemical parameters, such as pH, electrical conductivity (EC), sodium (Na+), potassium (K+), calcium (Ca2+), magnesium (Mg2+), chloride (Cl−), bicarbonate (HCO3), sulfate and total dissolved solids (TDS). Major hydrochemical facies were identified using Piper trilinear diagram. Furthermore, the results of the groundwater analysis were compared with historical measurements, showing changes in the chemical facies. Results highlight the possible irreversible negative effects on the ecosystem due to the geochemical evolution of lake water and groundwater.