Serum is known to be an essential evil for growth and development of any animal cells during culturing. Alternative serum replacement may be very costly, but because of very close composition of coconut water with serum, we first time have evaluated growth of BHK cell line in coconut water and serum as well. We find that coconut water can be used for growth of animal cell also but along with mixture. In coconut water, the growth rate of BHK cell line was 0.205 × 106 cells/ml/hrs while in 10% FBS the growth rate was 0.219 × 106 cells/ml/hrs. Media were optimized further for increasing overall cell growth rate. Therefore, optimized media containing coconut water using L18 design of Taguchi Design Of Experiment (DOE) methodology with seven media components such as FBS, Cell number, Coconut water, pH, Folic acid, rotation speed and NaHCO3 and finally we obtained the optimized conditions for overall growth of cells with 28% improvement in growth of cells BHK-21/c13 cell line.