The Einstein's mass-energy relation E = mc 2 is one of the most fundamental formulae in physics, but it has not been seriously tested by an elaborated experiment, and only some indirect evidences in nuclear reaction suggested that it holds to high precision. Manifestly, for a particle, different self potential leads to different energy-speed relation, which can be used as the fingerprints of them. In this letter, we propose an experiment to test this relation. The experiment only involves low energy of particles and measurement of speed, which can be easily realized. The experiment may shed lights on a number of fundamental puzzles in physics.Keywords: mass-energy relation, interactive potential, energy-speed relation In Einstein's original paper (Einstein, 1905), he derived the the kinetic energy of a particle K,which implies the total energy and the speed of a particle have the following relationHowever, the Einstein's derivation is based on the linear classical mechanics, and this relation has not been directly tested by elaborated experiment. (2) is actually p 0 of the 4-vector momentum but is different from the energy E in Nöther's sense for a particle with potential. There were once some indirect evidences in the nuclear reaction. The most accurate one is provided by Rainville et al. (2005), which indicates that the mass-energy relation E = mc 2 holds to an error level less than 0.00004% in the process of neutron capture by nuclei of sulfur and silicon resulting in γ-radiation. As pointed out by Bakhoum (2007), it is actually a test for the energy conversion ∆E = ∆mc 2 at low speed of the particles.Strange enough, as one of the most fundamental relation, a direct test for the energy-speed relation (2) is absent. It seems to be interesting for few people, and one can hardly find a literature involving the problem. As a matter of fact, this relation is related with a number of fundamental problems in physics, such as the relationship between quantum mechanics and classical one, the self-potentials of an elementary particles, the Lorentz transformation law for different parameters and Lorentz violation, the structure of the space-time etc. The main purpose of this letter is to draw the attention of physical society towards this problem.The Dirac equation with different potentials describes elementary particles, and maybe give some explanations for dark matter and dark energy (Gu, 2007a;Gu, 2008;Gu, 2017;Adanhounme, Adomou, Codo, & Hounkonnou, 2012;Ribas, Devecchi, & Kremer, 2005;de Vega, 2007;Vacaru, 2015). For spinors with self-potentials such as nonlinear potential and electromagnetic one A µ , detailed calculation shows the potentials result in different energy-speed relations, which can be used as fingerprints of the interactions. In classical mechanics, these relations are concealed. Taking c = 1 as unit of speed, we find the general representation of the energy-speed relation takes the following form (Gu, 2007b,c),where (M 0 , M 1 , M F ) are all constants of mass dimension, and M 0 is the total...