The separation of active organic molecules is the most challenging in pharmaceutical and petrochemical industries due to the intensive energy consumption of traditional distillation and the deactivation of active molecules during phase transition. Although the organic solvent nanofiltration (OSN) with nanoscaled molecular- separation ability is increasingly attractive for active organic molecule separations, the relatively low solvent permeance precludes OSNs from wide applications. Herein, we developed a kind of advanced mixed matrix membranes (MMMs) with both high permeances and high rejection by incorporating TiO2 into polypyrrole (PPy) selective layer through in- situ hydrolysis of Ti(OC4H9)(4) precursor on the surface of moisturized substrates. Owing to the uniform dispersion of in- situ formed TiO2 nanoparticles, positive tuning effects of Ti(OC4H9)(4) hydrolysis on PPy polymerization and structural characteristics of the hybrid selective layer, the in-situ TiO2 incorporated PPy MMMs demonstrate both high ethanol permeances as 16.2 L m(-2) h(-1) bar(-1) and high brilliant blue rejection (MW= 792.85 g mol(-1)) as 92%. Most importantly, the advanced membrane also demonstrates the ethanol permeance over 8.0 L m(-2) h(-1) bar(-1) during the long-term running test which is even higher than the initial permeances of many organic solvent nanofiltration membranes with similar rejection and high stability.