Background: Manipulators for robots are required to have high manipulability for adaptability in different tasks. However, general methods for designing manipulators with high manipulability are deficient. Here, aiming at improving the manipulability of the six degrees-of-freedom (DOF) manipulator, a method for optimizing structure size parameters based on the dexterous workspace volume is proposed. Methods: Firstly, the kinematic analysis of the manipulator is performed. Then, the manipulability of the single working point of the manipulator is judged based on reachability in different postures. The workspace of the manipulator is discretized to obtain the volume of the overall dexterous workspace. By taking the maximum volume of the dexterous workspace as the optimization goal, Genetic Algorithm (GA) is used to optimize the structure size parameters to achieve optimal manipulability. AUBO 6-DOF manipulator is defined and analyzed as an example. Results: The optimization results indicate that the dexterous workspace of the manipulator expands in volume and its manipulability is improved. The validity of the proposed optimization method is verified by comparing the distribution of dexterous workspace of the manipulator. Conclusions: This article proposes an optimization method for the structure size parameters of a 6-DOF manipulator, which can be implemented to improving the manipulability of the manipulator.