To set up the lay out monitoring points scientifically and reasonably for comprehensive management of watershed, the Fuhe River basin was taken as an object. Cluster analysis method was adopted to optimize the monitoring layout. The rationality analysis of layout optimization was carried out by combining relative deviation analysis with variance analysis, and the optimization scheme of monitoring layout was constructed in the Fuhe River basin. According to the optimization scheme of monitoring layout, two monitoring points were set up in the upstream, middle and downstream of the river trunk respectively. One monitoring point was set up in the upstream and downstream for the larger tributaries, and for smaller rivers only one monitoring point was set up at the river confluence. The results show that after optimization, monitoring points were reduced from 40 to 16, accounting for 40% of the initial monitoring points. The optimized points still cover the upper, middle and lower reaches, trunk and tributaries and important nodes of the Fuhe River basin. After optimization, the relative deviation of each category and index is small, and there is no significant difference between the indicators of each category before and after optimization.