Groundwater salinization and interaction between Playa Lake and regional groundwater were investigated using multi-chemo-isotopic evidences. Forty groundwater and 26 Kashan Playa Lake (KPL) water samples were collected and analyzed for their geochemical compositions. The evolution of hydrochemical facies in Kashan Plain Aquifer (KPA) to KPL is Ca-HCO3 (19%), Mix Ca-Cl (9%), Ca-Cl (17%), and Mix Na-Cl and Na-Cl (55%). Also, the Hydrochemical Facies Evolution Diagram (HFE-D) proposed cation exchange as the main process of salinization in KPA. Based on the binary hydrogeochemical diagrams of (Na+/Cl-)/Cl-, (Ca2+ + Mg2+)/HCO3- + SO4(2-), and Cl/Br, dissolution of halite and gypsum in the Miocene marlstone in the KPA is the main source of salinity. The delta O-18 of water in aquifer and playa water samples varies from -10.03 to 7.03 parts per thousand (VSMOW) with an average of -6.95 parts per thousand and -60.73 to 25.08 parts per thousand with average of -45.82 parts per thousand for delta H-2. Based on the results, the relation between delta O-18 and delta H-2, and delta O-18 and Br, approves discharge of saline water from KPA to KPL. Likewise, the isotopic composition of delta(SO4)-S-34, varies from 5.95 to 22.55 parts per thousand CDT in KPA, and 5.95 to 9.99 parts per thousand CDT in KPL. Also, the relations between delta O-18-delta S-34(SO4) and Cl-delta S-34 were non-linear, indicating that sulfur concentration in KPA and KPL changed due to sulfide oxidation and sulfate reduction in the freshwater and deep brines in the aquifer and mixed during the over-pumping in the KPA. Oxidation of sulfide minerals in the mineralized region in the western part of the aquifer (recharge zone) may have been the source of sulfur leached by seasonal runoff. Water-rock interaction, ion exchange, and hydraulic gradient have been the dominating factors in changing the water chemistry between aquifer and playa leading to saline groundwater discharged to the playa.