We describe the phase-transfer biocatalytic process for methane-to-methanol conversion based on the spontaneous phase-separable membrane micro-CSTR (lCSTR). The developed system has several critical benefits for operating the conversion reaction, including (a) preventing the whole-cell biocatalyst loss while operating the reactor continuously, (b) introducing a powerful mixing effect to significantly improve the mass transfer efficacy of methane to the biocatalyst, (c) facilitating the product separation process by employing the spontaneous phase separation system, and (d) providing an excellent platform for more complex, high-value-added conversion reactions.