Promising advances in membrane technology can lead to energy-saving and eco-friendly solutions in industrial sectors. This work demonstrates a highly selective membrane with ultrathin and highly interconnected organosiloxane polymer nanolayers by initiated chemical vapor deposition to effectively separate solutes within the molecular weight range of 150-300 g mol-1. We optimize the poly(1,3,5,7-tetravinyl-1,3,5,7-tetramethylcyclotetrasiloxane) membrane by adjusting both the thickness of the selective layer and the pore sizes of its support membranes. Notably, the 29 nm selective layer imparts a uniformly narrow molecular sieving property, providing a record-high solute-solute selectivity of 39.88 for different-sized solutes. Furthermore, a solute-solute selectivity of 11.04 was demonstrated using the real-world active pharmaceutical ingredient mixture of Acyclovir and Valacyclovir, key components for Herpes virus treatment, despite their molecular weight difference of less than 100 g mol-1. The highly interconnected membrane is expected to meet rigorous requirements for high-standard active pharmaceutical ingredient separation.,The use of membranes under harsh conditions, particularly involving the separation of complex organic solvents, remains challenging. Here the authors demonstrate an ultrathin organosiloxane polymer membrane using initiated chemical vapor deposition to effectively separate solutes within the molecular weight range of 150-300 g mol-1.,