In this study, a PLA foam was prepared by compression molding. The effect of three molding parameters was studied which are: the foaming time, mold opening temperature, and the weight content of the blowing agent. The desired open-cell foam morphology and average cell size were investigated and optimized. The Design of Experiments (DoE) was based on three design levels and response surface. A second-order polynomial model was developed from the DoE and used to predict the optimum three molding parameters presented above. For a mold opening temperature fixed at 100°C, the optimum foaming time and wight content of the foaming agent were 15 min and 7.7 wt. %, respectively.