This study aimed to optimize the culture conditions (agitation speed, aeration rate and stirrer number) of hyaluronic acid production by Streptococcus zooepidemicus. Two optimization algorithms were used for comparison: response surface methodology (RSM) and genetic programming coupling Quantum-behaved particle swarm optimization algorithm (GP-QPSO). In GP -QPSO approach, GP is employed to model the microbial HA production and QPSO algorithm is used to find out the optimal culture conditions with the established GP estimator as the objective function. The maximum predicted value of HA production by RSM and GP-QPSO was 5.27 and 5.57 g/l, respectively. Here though both RSM and GP-QPSO approach provided good predictions, yet the proposed GP-QPSO method showed a clear superiority over RSM for both data fitting and optimization capabilities