Tuned liquid column damper (TLCD) has been used extensively to improve the seismic behavior of structures, and different methods have been proposed for optimal design of TLCDs on linear structures. For improving the effectiveness of TLCDs, multiple tuned liquid column dampers (MTLCDs) have been proposed, and each TLCD has different dynamic parameters. In this paper designing optimal MTLCDs and assessment of its effectiveness in mitigating the response of structures under earthquake excitations have been studied. The parameters of TLCDs have been determined based on minimizing the maximum displacement of structure through solving an optimization problem. Genetic algorithm (GA) has been used for solving the optimization problem. For illustration, the method has been used for designing optimal MTLCDs for a ten-storey linear shear frame subjected to a white noise excitation. According to the results of numerical simulations it could be said that the proposed method for designing optimal MTLCDs has been effective regarding the simplicity and convergence behavior of the method. Based on designing MTLCDs for different values of MTLCDs total mass ratio, it has been concluded that MTLCDs total mass affects significantly the performance of MTMDs where its increasing has led to improve MTLCDs performance. Also, testing the optimal MTLCDs structure under different testing excitations has shown that the performance of MTLCDs depends on the characteristics of earthquakes.