Due to sand mining, the study objective is to assess water quality in the Progo River, Daerah Istimewa Yogyakarta Province. It is beneficial to evaluate the physicochemical parameters of the Progo River and to appraise water quality for drinking purposes based on the Indonesia Minister of Health regulation No: 492/ Menkes/Per/IV/2010. The physicochemical parameters used in this study included pH, EC, TDS, DO, SO4 2-, NO3-, and PO4 3-. The pH decrease is thought to be due to the opening of sand deposits around the river so that minerals such as feldspar, hornblende, and quartz dissolve and mix in water. The TDS increase was estimated due to the increase in the riverbed and bank erosion associated with sand mining at the mining and downstream sites. In addition, sand mining activities affect higher DO because bubbles aerate flowing water in fast-moving water as it churns over rocks and falls into hundreds of tiny waterfalls. Meanwhile, other parameters, such as EC, SO4 2-, NO3-, and PO4 3- are influenced by natural factors, such as seawater mixing and soil erosion. Almost all parameters are permissible for drinking purposes, except for Station 3 at the downstream which TDS and SO4 2-- values are.