Deformation under external and clamping forces is an important factor affecting fixture performance. To reduce the deformation of the workpiece–fixture system and improve the performance of the fixture, an optimisation method for the fixture layout and clamping force plan is constructed in this article. First, the workpiece–fixture is illustrated as an elastic–elastic contact model with friction in which the workpiece is modelled by the finite element model, while the fixel can be modelled by either the spring model or finite element model. To accelerate the computing speed of solving the contact problem, a matrix size reducing method for the finite element model stiffness matrix is proposed, utilising less computer memory. Based on the same idea, a clamping force optimisation method considering the friction effect is presented to achieve the optimal clamping force of a special fixture layout within very few finite element model computing processes. Then, based on these, an integral fixture layout and clamping force optimisation algorithm are built by genetic algorithm. At the end of this article, numerical examples are taken to prove the performance of the methods. The results show that the accelerating method yields sufficient performance, and the optimisation algorithms of both the clamping force plan and the fixture layout design achieve favourable convergence.