The airfoil optimization design based on numerical calculation of aerodynamic performance can reduce the cost and shorten the design cycle, which has gradually become the mainstream of airfoil design. This paper presents an optimization method of airfoil based on potential flow model with isogeometric collocation method. Firstly, the velocity potential of the potential flow model under an ideal incompressible flow is solved by using the isogeometric collocation method. Secondly, the aerodynamic characteristic index of airfoil, e.g. lift-to-drag ratio, is calculated based on the Blade Element Theory. Finally, an objective function containing the maximum lift-to-drag ratio and the minimum fitting error is constructed to ensure the aerodynamic performance and smoothness of the airfoil. The optimized airfoil is obtained by utilizing a variety of optimization methods. In the experiment, the NURBS representation of the initial airfoil was acquired by fitting the data points of three types of airfoil by the Progressive Iterative Approximation method. The optimization results show that the algorithm not only keeps the airfoil's own characteristics and smoothness, but also improves the index of lift-to-drag ratio significantly.