The Kızılırmak River is the longest river (1.355 km) in Turkey and flows into the Black Sea. Main pressures in the basin are waste water discharges, widespread agriculture, livestock activities, and excessive salinity due to the natural formation. In this study, the performance of the most widely used European diatom indices (IPS, IDG, IBD, EPI-D, TDI, and TI) was tested statistically by comparing them with the indicators of organic pollution (biological oxygen demand and ammonium-nitrogen), eutrophication (orthophosphate and nitrate-nitrogen) and salinization (electrical conductivity) in the Kızılırmak basin, Turkey. For this purpose, a total of 97 diatom samples from 33 rivers were collected seasonally in 2014 and 215 species were identified. Principal component analysis was performed to evaluate the “general degradation” in the basin, and linear regression was used to calculate the correlations with diatom indices. As a result, EPI-D, IPS, IBD, and TI were strongly correlated indices, respectively, while IDG and TDI had the lowest correlations with general degradation. Only the EPI-D index was significantly correlated with all environmental variables. Our results showed that the EPI-D index can be used for the ecological status assessment in terms of phytobenthos in the Kızılırmak basin in line with the Water Framework Directive.