Groundwater salinization and interaction between Playa Lake and regional groundwater was investigated using multi-chemo-isotopic evidences. Forty groundwater and 26 Kashan Playa Lake (KPL) water samples 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-+SO42-, and Cl/Br, dissolution of halite and gypsum in the Miocene marlstone in the KPA is the main source of salinity. The isotopic composition δ18O in aquifer and playa water samples varies from -10.03 to 7.03‰ (VSMOW) with an average of -6.95 ‰ and -60.73 to 25.08 ‰ with average of -45.82 ‰ for δ2H. Based on the result, the relation between δ18O and δ2H, and δ18O and Br, approve discharge of saline water from KPA to KPL. Likewise, the isotopic composition of δ34SO4, varies from 5.95 to 22.55 ‰ CDT in KPA, and 5.95 to 9.99 ‰ CDT in KPL. Also, the relation between δ18O- δ34SSO4 and Cl- δ34S were non-linear, indicating that sulphur concentration in KPA and KPL changed due to sulphide oxidation and sulphate reduction in the freshwater and deep brines in the aquifer and mixed during the over-pumping in the KPA. Oxidation of sulphide minerals such as galena (PbS), and Chalcopyrite (CuFeS2) may have been the source of sulfur in Dore mine in western part of the aquifer (recharge zone) leached by seasonal runoff. In general, 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.