Thermodynamic analysis, especially the second-law analysis; has been applied in engineering design and optimization of microscale gas flow and heat transfer. However, following the traditional approaches may lead to decreased total entropy generation in some microscale systems. The present work reveals that the second-law analysis of microscale gas flow and heat transfer should include both the classical bulk entropy generation and the interfacial one which was usually missing in the previous studies. An increase of total entropy generation will thus be obtained. Based on the kinetic theory of gases, the mathematical expression is provided for interfacial entropy generation, which shows proportional to the magnitude of boundary velocity slip and temperature jump. Analyses of two classical cases demonstrate validity of the new formalism. For a high-Kn flow and heat transfer, the increase of interfacial transport irreversibility dominates. The present work may promote understanding of thermodynamics in microscale heat and fluid transport, and throw light on thermodynamic optimization of microscale processes and systems. (C) 2016 Elsevier Ltd. All rights reserved.