The application of the mean force field in protein mutant stability prediction is explored. Based on protein main chain characteristics, including polar fraction, accessibility and dihedral angles, the mean force field was constructed to evaluate the compatibility between an amino acid residue and its environment, from which a position-dependent protein mutant profile was constructed. At each position along a protein sequence, the native residue was replaced by the other 19 types of amino acid residues. The matches were evaluated by energies from mean force field calculation, from which a mutant profile along the protein sequence was derived. General characteristics of such a profile were analyzed. Mutant stabilities for two sets of mutants in two proteins were found to be reasonable compared with experimental data, which indicates that the present method can act as a guide in protein engineering and as an effective scoring matrix in protein sequence-structure alignment studies.