The relative occurrences of amino acids, residual properties, and secondary structure type found in the residual structure states were compared between thermophilic and mesophilic proteins to find out the protein-thermostabilizing factors. The thermostabilizing patterns in each residual structure state are as follows: (1) in fully exposed state, higher relative occurrences of GLN, ILE, and PHE; (2) in exposed state, higher relative occurrences of ARG, GLU, salt bridges, the residue with low solvation energy, and the residues in 3/10 helix, and lower relative occurrences of ALA, SER, and VAL; (3) in partially exposed state, higher relative occurrence of flexible residue and lower relative occurrence of SER; (4) in buried state, higher relative occurrences of ARG and GLU, and lower relative occurrence of MET; and (5) in well-buried state, higher relative occurrences of ALA, cation-pi interaction, the residues in 3/10 helix, and lower relative occurrences of ASP, GLY, and the residues in the extended beta strand. These findings could be useful for developing protein thermostabilization strategies according to each residual structure state.