We consider the problem of output regulation for LTI systems in the presence of unknown exosystems. The knowledge about the multi-frequency signals exosystem consists in the maximum number of frequencies and their maximal value. The control scheme relies on two main components: an estimation algorithm, to reconstruct the signal generated by the exosystem, and a controller, to enforce the output regulation property to the closed-loop system. To tackle the first task, we propose a hybrid observer for the estimation of the (possibly piece-wise continuous) number and values of the frequencies contained in the exogenous signal. The hybrid observer is particularly appealing for numerical implementations, and it is combined with a self-tuning algorithm of the free parameters (gains), thus improving its performance even in case of noisy measurements. Semi-global exponential convergence of the estimation error is provided. As far as the second task is concerned, a robust hybrid regulator is designed for practical rejection of the multi-frequency disturbance signal acting on the plant. The result is achieved by exploiting the frequencies estimated by the hybrid observer. The effectiveness of the proposed control scheme is shown by means of numerical simulations.