In order to meet the requirements of filtering performance and multi-parameter optimization of liquid crystal tunable filter (LCTF), an optimal design method of Lyot type LCTF based on the artificial immune algorithm (IA) is proposed in this paper. This method takes the basic spectral performance of Lyot type LCTF such as optical transmittance, full width at half maximum (FWHM) of the transmitted main peak, and sidelobe suppression (SLS) in cut-off region as the evaluation function,which aims to find optimal configuration of liquid crystal cells’ thickness and driving voltages of LCTF based on global range constrained by specific evaluation function. The simulation results show that compared with the traditional Lyot type LCTF, the side lobe suppression effect of the optimized LCTF by IA algorithm is increased by 73.42% and the overall filtering effect is improved by 13.90%. At the same time, this method can realize the intelligent regulation of the filter performance only by adjusting the weight ratio of parameters in the evaluation function to meet the requirements of different application scenarios. The most attractive advantage of this design method is that it can avoid the serious dependence of the traditional filters on the linear accuracy of device thickness. Moreover, it is not only more flexible in selection of liquid crystal cells thickness and numbers, but also can improve the spectral response time and optical transmittance, which ensures the high efficiency,development practicality and economy.