In this paper we report a bio-synthesis participated route towards controllable mesoporous LiFePO4/C nanocomposite microspheres (MP-LFP/C-NC-MS). During the synthesis Baker’s yeast cells are used as both structure templates and carbon source. Then we clarify the bio-deposited and biomolecular self-assembly mechanisms of iron phosphate by means of the Langmuir biosorption isotherms of the yeast biomass in iron ion solution and by applying the model of heterogeneous nucleation of iron phosphate in yeast cell. The MP-LFP/C-NC-MS show a uniform size distribution (4.76 μm), high tap density (1.74 g cm-3) and large specific surface area (203 m2 g-1). The microsphere is composed of densely aggregated nanoparticles and interconnected nanopores. The open mesoporous structure allows lithium ions easily to penetrate into the spheres, while a thorough coating of the biocarbon network on the surface of the LiFePO4 nanoparticles facilitates lithium ion and electron diffusion. The MP-LFP/C-NC-MS have high discharge capacity of about 158.5 mA h g−1 at the current density of 0.1 C, discharge capacity of 122 mA h g−1 at 10 C, and high capacity retention rate. Therefore the mesoporous microspheres are an ideal type of cathode-active materials for making high-power Li-ion batteries.