We study the influence of running vacuum on the baryon-to-photon ratio in running vacuum models (RVMs). When there exists non-minimal coupling between photons and other matter in the expanding universe, the energy-momentum tensor of photons is no longer conserved, but the energy of photons could remain conserved. We discuss the conditions for the energy conservation of photons in RVMs. The photon number density and baryon number density, from the epoch of photon decoupling to the present day, are obtained in the context of RVMs by assuming that photons and baryons can be coupled to running vacuum, respectively. Both cases cause the baryon-to-photon ratio to no longer be a constant. However the evolution of the baryon-to-photon ratio is strictly constrained by observations. It is found that if the dynamic term of running vacuum is indeed coupled to photons or baryons, the coefficient of the dynamic term must be extremely small, which is unnatural. Therefore, our study basically rules out the possibility that running vacuum is coupled to photons or baryons in RVMs.