In modern industrial applications, robot has become one of the most important parts, which has significant application prospects in the fields of simulation, logistics and machine processing. Actually, compared with parallel mechanisms’ compact structure, higher load capacity and higher stiffness, serial robots have the advantages of bigger workspace and easier control, which can be complementary with parallel mechanisms. Thus, hybrid manipulators, especially 5-degree-of-freedom (DOF) hybrid manipulators, combine the merits of both serial robots and parallel mechanisms. Firstly, the structure description of a novel 5-DOF hybrid manipulator was done. The parallel part of the hybrid manipulator 2RPU/UPR contained two continuous rotational axes. Secondly, the dimension optimization of the 5-DOF hybrid manipulator was introduced in detail. Then, mechanical design and analysis about the main parts of the hybrid manipulator were finished, and structure optimization was performed. Finally, finite element simulations considering different positions and orientations were achieved. The results before and after optimized hybrid manipulator were analyzed, which showed that the stiffness of the optimized manipulator was improved and the mass of it was reduced. The 5-DOF hybrid manipulator had the characteristics of owning continuous rotational axes, simple structure and less single DOF joint, which allowed for a very variety of application prospects. More importantly, the research would enhance the research applications of robot and lay good theoretical foundations for the application of this novel manipulator.