In the 1930s he studied the ion exchange processes between aqueous solutions and solids.

During that time Nikolsky developed the theory of ion exchange in glass electrodes.

He derived equations that describe properties of glass electrodes as well as other types of ion-selective electrodes depending on chemical structure and multi-component composition of glass, concurrent interference of ions (see Nikolsky-Eisenman equation and Nikolsky-Shultz-Eisenman thermodynamic ion-exchange theory of GE[1][2][3][4]) and so on.

Boris Nikolsky also actively participated in the Soviet nuclear program.

In 1952-1974 he was the senior scientist and the chairman of scientific committee at the Soviet nuclear fuel reprocessing plant Mayak, where he worked on the technology of processing and refining of plutonium.