This hydrogeochemical research was conducted to improve the understanding of (1) groundwater flow and its hydrochemical evolution in a complex karst-fissured aquifer system, and (2) the interaction between groundwater and water transported via hydraulic tunnel of the hydropower plant (Pirot, Serbia). The tunnel traverses the main fault zones between two regionally important tectonic units, Getic and Danubian, allowing deep groundwater circulation and higher infiltration of groundwater into the tunnels. Water samples were collected at the surface and within the tunnels in four different sampling campaigns, depending on the tunnel operational regime in 2016, and measurements of physicochemical parameters (pH, ORP, EC, T) and groundwater sampling for chemical analysis (Ca, Mg, Na, K, Sr, Li, HCO3, SO4, Cl, NO3, H2S) were conducted. This was a unique opportunity to investigate hydrochemical processes based on groundwater leakage along the tunnel profile line. The main problem is compounded by the fact that it is a hydraulic tunnel that transports water under pressure, thereby interacting with the hydrogeological environment. Changes in the tunnel operational mode cause hydraulic changes in the hydrogeological environment, which is a key part of this research. The presence of different hydrochemical facies appearing in the tunnel (from Na–Cl through Na-HCO3 to Ca(Mg)–HCO3 water types) pointed to the complexity of the hydrogeological system in the shallow, and deep groundwater flow systems developed in karst and fissured aquifer. Heterogeneity of bedrock had an important influence on the hydrochemical conditions accompanied by processes revealed through hydrochemical and multivariate statistical analysis: hierarchical cluster analysis (HCA) and principal component analysis (PCA). The main processes are defined as (1) dissolution processes in hypogenic conditions of the karst hydrogeological system, associated with high mineralization of groundwater, (2) cation exchange process, (3) the dissolution of different types of carbonate bedrock. A combined approach of multivariate statistical analysis and standard hydrochemical methods enabled the separation of groundwater with the highest compositional changes as points of the strongest artificial influence in the narrow tunnel zone.