Modulated membrane functionalization is a necessary and overarching step for hollow microcompartments toward their application as nanoreactors or artificial cells. In this study, we show a way to generate phospholipid hybrid proteinosomes that could show superposed virtues of liposomes and proteinosomes. In comparison to pure proteinosomes, both the membrane fluidity and permeability are improved obviously after forming the phospholipid hybrid proteinosomes. Specifically, the integration of phospholipids also endows the hybrid proteinosomes demonstrating a stepwise release of the encapsulants of FITC-dextran (70 and 150 kDa) triggered sequentially by phospholipase and protease, and then a modulated cascaded enzymatic reaction between two different populations of proteinosomes are achieved. Therefore, it is anticipated that such constructed phospholipid hybrid proteinosomes could be employed as an improved microcompartmental model for further advanced artificial cell design toward achieving logic signal communication within the various artificial cellular populations as well as potential applications in the field of microreactors.