Uncertainties are ubiquitous and unavoidable in process design and modeling while they can significantly affect safety, reliability, and economic decisions. The large number of uncertainties in complex chemical processes make the well-known Monte-Carlo and polynomial chaos approaches for uncertainty quantification computationally expensive and even infeasible. This study focused on the uncertainty quantification and sensitivity analysis of complex chemical processes with a large number of uncertainties. An efficient method was proposed using a compressed sensing technique to overcome the computational limitations for complex and large scale systems. In the proposed method, compressive sparse polynomial chaos surrogates were constructed and applied to quantify the uncertainties and reflect their propagation effect on process design. Rigorous case studies were provided by the interface between MATLAB (TM) and Aspen HYSYS (TM) for a propylene glycol production process and lean thy gas processing plant. The proposed methodology was compared with traditional Monte-Carlo/Quasi Monte-Carlo sampling-based and standard polynomial chaos approaches to highlight its advantages in terms of computational efficiency. The proposed approach could mitigate the simulation costs significantly using an accurate, efficient-to evaluate polynomial chaos that can be used in place of expensive simulations. In addition, the global sensitivity indices, which show the relative importance of uncertain inputs on the process output, could be derived analytically from the obtained polynomial chaos surrogate model. (C) 2016 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.