We propose a novel experimental approach to explore exotic spin-dependent interactions using a spin-exchange relaxation-free (SERF) magnetometer, the most sensitive non-cryogenic magneticfield sensor. This approach studies the interactions between optically polarized electron spins located inside a vapor cell of the SERF magnetometer and unpolarized or polarized particles of external solid-state objects. The coupling of spin-dependent interactions to the polarized electron spins of the magnetometer induces the tilt of the electron spins, which can be detected with high sensitivity by a probe laser beam similarly as an external magnetic field. We estimate that by moving unpolarized or polarized objects next to the SERF Rb vapor cell, the experimental limit to the spin-dependent interactions can be significantly improved over existing experiments, and new limits on the coupling strengths can be set in the interaction range below 10 −2 m.Recently, exotic spin-dependent interactions, predicted by string theories and many theoretical extensions of the Standard Model of particle physics [1][2][3], have attracted much attention in the community of physicists. Such theories are associated with the spontaneous breaking of continuous symmetries, leading to massless or very light Nambu-Goldston bosons [4][5][6], such as the axion [7], and axion-like-particles (ALPs) [2,8], which are candidates for cold dark matter [9,10]. These exotic particles are bosons and can weakly couple with ordinary particles, such as leptons or baryons. Moody and Wilczek [11] first proposed three possible types of interactions between polarized and unpolarized particles, which were later expanded by Dobrescu and Mocioiu [12] with the inclusion of the terms dependent on the relative velocity between the two interacting particles. A general classification of the interactions between particles contains sixteen types of structure of operators: fifteen of them depend on the spin of at least one of the particles and seven depend on the relative velocity of the particles. In this paper, we show a new experimental method to explore all the fifteen exotic spin-dependent interactions.The possible exotic spin-dependent interactions between polarized and unpolarized particles are (in SI units, where m p is the mass of the polarized particles,σ i is the spin vector of the i th polarized particle while σ i = σ i /2, is Planck's constant,r = r/r is a unit vector in the direction between the polarized and unpolarized particles, v is their relative velocity, c is the speed of light in vacuum, and λ is the interaction range.There are nine interactions between two polarized particles, three of which are not dependent of the relative velocity of the particles v,