Differential problems with the Riesz derivative in space are widely used to model anomalous diffusion. Although the Riesz–Caputo derivative is more suitable for modeling real phenomena, there are few examples in literature where numerical methods are used to solve such differential problems. In this paper, we propose to approximate the Riesz–Caputo derivative of a given function with a cubic spline. As far as we are aware, this is the first time that cubic splines have been used in the context of the Riesz–Caputo derivative. To show the effectiveness of the proposed numerical method, we present numerical tests in which we compare the analytical solution of several boundary differential problems which have the Riesz–Caputo derivative in space with the numerical solution we obtain by a spline collocation method. The numerical results show that the proposed method is efficient and accurate.