Multi-parameters of physiological metabolism, environmental state, cell morphology, and manipulated variable, have mutual influences and constraints on coenzyme Q ₁₀ (CoQ ₁₀) biosynthesis of Rhodobater sphaeroides. In this work, a multi-parameter fusional correlation-analysis were applied to illuminate and optimize the crucial metabolism on CoQ ₁₀ biosynthesis. The quantitative response model for accurate living cells concentration, morphological deformation, specific oxygen consumption rate (Q _O2), and specific product biosynthesis rate were established, the results revealed that maintain the optimal electrical conductivity(Cond.) and Q _O2 at 9.0±0.5 mS/cm and 0.06-0.08±0.01×10 ^-7mmol/cell/h, respectively, by adjusting the nutrient feeding and oxygen transfer rate, the cell’s morphology and oxygen uptake rate were strengthened. CoQ ₁₀ production in 50L bioreactors was successfully improved by 35% to 3384mg/L than that of control, which would be more powerful and effective for scale up in the large-scale production of CoQ ₁₀.