Recent advances in technologies of reactive distillation (RD) offer various design concepts for chemical processes. For separation of cracking C5 fraction, one of the main challenges is improving the conversion of cyclopentadiene (CPD) and the recovery of isoprene (IP). In the current work, a novel reactive distillation column with several liquid-holdup regions was designed, since it allows long residence time and provides flexibility for narrowing the efficiency gap between reaction and distillation. By use of Aspen Plus, a corresponding mathematic model was established and verified to be accurate. Following that, comprehensive studies were carried out for the design of liquid-holdup regions position. Details and principles about the separation performance with the liquid-holdup regions were revealed and optimized parameters were determined with 100 theoretical plates, feed position of 35th plate, and four liquid-holdup regions at 25th, 60th, 75th and 90th plate. The designed RD column could wellmeet the technical requirement, and influence of other important factors including residence time, operating pressure and reflux ratio was further investigated. (C) 2016 The Chemical Industry and Engineering Society of China, and Chemical Industry Press. All rights reserved.