The aim of this study was to evaluate the quality of the Tisa River on its flow through Serbia. The water quality status and the spatial and temporal trends along the Tisa River were assessed through the application of ten SWQI parameters derived from a six-year public database of environmental data (2011-16). Also, the created data set was treated by multivariate techniques in order to identify the similiraties and differences between sampling periods and locations, recognize variables that affect the temporal and spatial water quality and present anthropogenic impact on water quality parameters. This study reveals that water quality along the Tisa River decreases slightly downstream. Obtained values of SWQI descriptive quality indicator indicated that water quality on this course, during the monitoring period, was good (72-83) and very good (84-89). Multivariate statistical techniques (PCA/FA) led to the conclusion that the changes in water quality mostly occur under the influence of organic pollutants (anthropogenic) and nutrients (total phosphorus, ammonia, etc.).