As the half-wave potential is an important electrochemical property used for the characterization of organic compounds, this study is aimed to build up a QSPR model of half-wave oxidation potential of 4-(benzylsulfanyl)pyridines. Firstly, mechanism of electrochemical oxidation of 4-(benzylsulfanyl)pyridines as a model of their possible metabolic degradation was elucidated by preparative electrolysis and GC-MS analysis of oxidative products. Secondly, the QSPR of a half-wave potential of 4-(benzylsulfanyl)pyridines has been performed by two computational approaches: (i) optimal descriptors calculated with Simplified Molecular Input Line Entry System (SMILES), and (ii) classical Hammett constants. Both models have been proved to be statistically significant, and the statistical qualities of both computational approaches are comparable. The mechanistic interpretations of both approaches have been given, and their results gave complementary views on effect of structure of molecular fragments of substituents on the half-wave potential of examined compounds. (C) 2016 Elsevier B.V. All rights reserved.