Purpose This study aims to numerically analyze natural convection of alumina-water nanofluid in a differentially-heated square cavity partially filled with a heat-generating porous medium. A single-phase nanofluid model with experimental correlations for the nanofluid viscosity and thermal conductivity has been considered for the description of the nanoparticles transport effect in the present study. Local thermal non-equilibrium approach for the porous layer with the Brinkman-extended Darcy model has been used. Design/methodology/approach Dimensionless governing equations formulated using stream function, vorticity and temperature have been solved by the finite difference method. The effects of the Rayleigh number, Ostrogradsky number, Nield number and nanoparticles volume fraction on nanofluid flow, heat and mass transfer have been analyzed. Findings It has been revealed that the dimensionless heat transfer coefficient at the fluid/solid matrix interface can be a very good control parameter for the convective flow and heat transfer intensity. The present results are original and new for the study of non-equilibrium natural convection in a differentially-heated nanofluid cavity partially filled with a porous medium. Originality/value The results of this paper are new and original with many practical applications of nanofluids in the modern industry.