The present study investigated the influence of square microchannel (MC) size on hydrodynamics and mass transfer in the liquid‐liquid slug flow regime. Three square MCs with the hydraulic diameters of 200, 400, and 600 μm were used. The employed method for estimating mass‐transfer coefficients remarkably increased the accuracy of the results. The findings revealed that decreasing the MC size improved the interfacial area due to plug length enlargement and deteriorated mass‐transfer resistances because of augmented internal circulations, leading to the considerable enhancement of mass‐transfer coefficients. The increasing effect on the overall mass‐transfer coefficient became greater with flow velocity, showing that size effect on mass‐transfer resistances was more profound at higher flow velocities. The influence of size on the interfacial area was significantly greater than that on mass‐transfer resistances due to the significant increment of wall film length with the decrease in channel size. © 2017 American Institute of Chemical Engineers AIChE J, 2017