A　thermodynamic　model　was　developed　based　on　the　first　principles　to　describe　the　thermal　stability　in　the　phase-separated　alloy　systems.　The　distributions　of　the　solute　atoms　in　the　nanocrystalline　system　were　predicted　for　the　heating　process,　using　the　typical　phase-separating　system　of　W-Cr　alloy　as　an　example.　The　effects　of　the　re-dissolution　and　grain-boundary　segregation　processes　on　the　thermal　stability　of　the　nanograin　structure　were　investigated,　based　on　which　the　critical　conditions　of　grain　size　and　solute　concentration　for　controlling　destabilization　of　nanostructure　at　high　temperatures　were　proposed.　The　transformation　of　solute　distribution　from　phase　separation　to　grain-boundary　segregation　was　described　in　detail　by　the　present　model　without　introducing　any　empirical　parameters.　The　calculations　indicated　that　the　stabilization　mechanisms　are　distinct　for　the　single-　and　double-phase　states　of　the　nanocrystalline　alloys　even　at　the　same　composition.　Thus　the　approach　to　inhibit　nanograin　growth　is　flexible　by　adjusting　the　solute　distribution　to　reach　either　the　thermodynamically　stable　or　the　meta-stable　state.　This　study　advanced　the　understanding　of　the　doping　effect　and　facilitated　precise　design　of　nanocrystalline　alloys　with　high　stability　during　high-temperature　heat　treatment.　©　2021　Elsevier　B.V.