Background & Objectives: Monitoring and quality control of water resources are important tools to manage and protect these valuable resources. Hiroo River is the principal source of water supplies for Khalkhal and Kosar cities. The purpose of this work was to investigate water quality of Hiroo River by NSFWQI and WILCOX indices. Methods: In this descriptive cross-sectional study pH, DO, BOD, TS, NO3, PO4, turbidity, temperature, fecal coliform, EC, Na, K, Ca, and Mg were determined. NSFWQI and WILCOX indices were applied. Data were analyzed by determining the above mentioned quality indices. Results: In the optimum situation, NSFWQI was related to S1 with the value of 74 in February 2009 indicating good water quality. Minimum value of 53 was determined for NSFWQI at S3 in August 2009 representing medium water quality. Conclusion: Water quality was good in upstream (S1) due to lack of contamination sources, however, discharging wastewater of Khalkhal and Givi cities to the river decreased water quality gradually in downstream (S2 and S4). Average of data obtained indicates that all the monitoring stations fall in C (medium) category based on NSFWQI classification.