The synthesis of compounds in a multi-component system involving volatile elements remains a costly trial and error practice today, although the governing thermo-chemistry theory and relevant computer modeling tools are well-established. We report a design of synthesis routes based on thermodynamic principles and a fabrication of Cu2ZnSnSe4 (CZTSe) via a solvo-thermal method. To suppress the sublimation of Se, we make use of binary compounds of high vaporization temperature by first converting solid Se into a liquid-like alloy. To simulate the sublimation and vaporization behavior of the system, estimates of the liquid-phase Gibbs energy have to be first derived for the compounds SnSe, SnCu, SnZn and SnS using FactSage (a well-established computational thermo-chemistry platform). Finally, single-phase CZTSe compounds are successfully synthesized and characterized. The relationships among synthesis parameters, microstructure, optical band gap, and visible light absorption are analyzed based on thermodynamic principles. This thermo-chemistry aided research strategy is significant not only to general chemical synthesis involving volatile constituent(s) but also to a wide range of subjects in materials chemistry. (c) 2014 The Society of Powder Technology Japan. Published by Elsevier B.V. and The Society of Powder Technology Japan. All rights reserved.