Water samples were collected from river Indus over 591 km2 from Kashmor to Keti Bandar/Shah Bandar in the province of Sindh, Pakistan, during 2008 and 2009 on seasonal bases. These samples were analyzed for 12 water quality variables including physical and chemical parameters. Then correlation study was carried out and correlation co-efficient “r” was determined using correlation matrix to identify the highly correlated and interrelated parameters. Regression model were developed to test the significant ‘r’ and P-value test was carried out to test the significance of the pair of parameters. F-test was also used to examine the joint-effects of several independent variables without taking into account the separate effects of each variable. The comparison of the observed and predicted values of different parameters using regression equation suggested that the regression model provide useful means of rapid and easier monitoring of water quality of a river in a region.Key words: Regression model, correlation coefficient, river indus, monitoring, physico-chemical parameters