Fen River Basin (FRB) is water-deficient and strongly influenced by human activities in the eastern Chinese Loess Plateau. The spatio-temporal variation and controlling factors of hyrochemistry and quality, sources of high boron, sulfate, and nitrate of surface waters in FRB were unclear. Major ions, delta 11B, delta 15N, and delta 18O in surface waters in dry season and wet season of FRB were analyzed and correlation analysis (CA), principal component analysis (PCA), self-organizing map (SOM), forward model, and Bayesian isotope mixing model (MixSIAR) were used to solve above problems. Results showed that average riverine delta 11B, delta 15N, and delta 18O of FRB was 7.8%o, 11.2%o, and 1.3%o (1SD), respectively. Dissolved solutes ranked midstream > downstream > upstream with water type of Na +-Cl-, Ca2+-Mg2+-Cl-, and Ca2+-HCO3-, respectively. Low dissolved solutes were in forest areas while high values were in cropland and city areas. SOM analysis indicated that hydrochemistry was both influenced by natural (upstream) and pollutional input (midstream and downstream) and variation between dry season and wet season was minor. The abnormally high boron concentrations were mainly from silicate weathering (43%) and evaporites dissolution of loess (32%), urban and industrial input contributed 15% of riverine boron. High SO42- (207 +/- 267 mg/L, 1SD) was mainly from sulfates. delta 15N and delta 18O analysis indicated that nitrification was the primary N cycling process. Further, MixSIAR showed that NO3- was mainly from municipal sewage (-67%) and the total contribution of chemical fertilizer and soil nitrogen was -30% with slightly higher values in upstream and wet season. Influenced by land-use types, evaporite dissolution, and anthropogenic input, water quality below midstream was worse and strict sewage reduction policies must be developed. This study highlights the significant influence of evaporite dissolution of loess and anthropogenic input (urban and industrial input for B and sewage for NO3- ) on hydrochemistry and water quality.