Conventional hollow fiber models in process simulators usually assume constant membrane permeance i.e., independent of pressure and temperature. In this work, hollow fiber membrane model has been proposed to cater the effects of temperature and pressure on membrane permeance. The proposed model is incorporated with Aspen HYSYS as a user defined unit operation in order to study the performance of gas separation system. The simulated model is validated by experimental and published data. The temperature drop due to Joule Thomson effect and its contribution to the change in membrane permeance has also been investigated. Similarly, the effect of pressure on membrane permeance has been studied. The influence of these effects on the separation performance and process economics has been investigated for the separation of CO2 from natural gas. The proposed hollow fiber membrane model has potential to be applied for design, optimization and scale up of wide range of gas separation systems. © 2012 Elsevier B.V.