Abstract High-performance harvesting of waste heat energy and its conversion into electric energy via thermo-electrochemical cells is an essential strategy of renewable energy development. Even though there is a large amount of scientific research available, but due to expensive electrode materials and low efficiency, the thermo-electrochemical cells have not found practical application. Here we demonstrated thermo-electrochemical cell with nickel (Ni) hollow microspheres-based electrodes, provided the highest hypothetical Seebeck coefficient of 4.5 mV/K (for aqueous electrolyte based thermocells) until today and open-circuit voltage values of up to 0.2 V. High values of Seebeck coefficient provide the ability to collect low-temperature heat, and high output potential differences which allow to fabricate batteries for commercial power circuits for various microelectronic devices. This work also proposed a mechanism and science behind the electrode processes, which explains a extremely high values of the hypothetical Seebeck coefficient. This is the first time to use Ni hollow microsphere in thermo-electrochemical cell for heat harvesting and thermal energy conversion into electricity. Because of the low cost of Ni microspheres electrode-based developed thermo cells could be commercially feasible for harvesting low-quality thermal energy.