The objective of this study is to develop a separation process of propylene oxide (PO) from direct propylene epoxidation with H-2 and O-2 via solvent screening followed by process optimization, where PO absorption/ concentration/refinery and solvent recovery tower are involved. A comparison of absorption processes among 15 ethers/ketones/esters/aromatics solvents shows that propylene carbonate (PC), diethyl carbonate, and acetophenone are more appropriate absorbents because of their high PO/solvent recovery, absence of reactions/azeotropes, and low energy consumption. Process optimization is further performed for the outlet PO purity requirement, e.g., 99.98% of LyondellBassell. It demonstrates PC to be the most promising solvent, which can afford outlet PO/PC purity and recovery of 99.98%/100% and 99.94%/99.95%. Meanwhile, the solvent recovery tower has lowered stages by 5-14 and energy consumption by 2-3.5 times, respectively. Moreover, the developed separation process is also applicable for inlet components containing propane and acrolein. These results could guide the separation process design of PO from the direct propylene epoxidation with H-2 and O-2.