Quantum tunneling reactions in a general classical bath are studied. By invoking the semiclassical approximation, a general theoretical framework for an arbitrary quantum double-well reactive system, coupled to the anharmonic classical modes is developed in a strong tunneling regime. For illustration, a simple two-dimensional model proton transfer system in solution at room temperature is considered. It is found that the bath anharmonicity strongly modulates the overall rate constant and kinetic isotope effect. For the positive anharmonicity, the reaction rate decreases compared to the harmonic case, while the associated kinetic isotope effect increases. By contrast, the negative anharmonicity reduces the kinetic isotope effect, while it enhances the overall rate. The temperature dependence of the rate constant and kinetic isotope effect is also analyzed. Despite tunneling (k(H)/k(D)=10–40), the Arrhenius behavior for the rate constant is found, regardless of the bath anharmonicity. This clearly indicates a strong interplay between the quantum and classical modes of the system.