The　conceptual　design　and　systematic　comparison　of　S-CO2　coal-fired　power　generation　systems　are　performed　in　the　viewpoint　of　the　thermodynamic　analysis　and　economic　assessment　to　promote　the　practical　application　in　the　industry.　First,　the　differences　between　the　conventional　steam　boiler　and　S-CO2　boiler　are　pointed　out.　3　layouts　of　the　water-cooling　wall　are　compared　in　the　aspect　of　the　hydrodynamic　characteristic　and　structural　parameters　to　select　the　suitable　one　coupled　to　the　S-CO2　cycles.　Based　on　the　optimized　water-cooling　wall　layout,　the　energy,　exergy　and　economic　analysis　models　of　the　integrated　S-CO2　coal-fired　power　systems　are　further　developed.　Finally,　the　mechanism　of　the　inter-cooling　thermodynamic　process　to　improve　the　system　performance　is　investigated　and　the　distribution　of　the　individual　irreversibility　is　given.　The　systematic　comparison　is　performed　among　3　configurations　of　S-CO2　coal-fired　power　plants　with　consideration　of　the　thermo-economic　performance.　The　conceptual　design　of　key　components　is　also　provided.　The　results　demonstrate　that　the　S-CO2　boiler　is　fatter　due　to　8　times　larger　mass　flow　rate　of　working　fluid　than　the　conventional　steam　boiler.　The　layout　of　water-cooling　wall　with　the　split　flow　strategy　and　vertical　tubes　is　helpful　in　compacting　the　scale　of　the　boiler　for　its　less　diameter　and　number　of　tubes,　and　its　thermal　efficiency　is　higher　than　that　of　other　layouts.　Among　the　3　S-CO2　cycle　layouts　studied,　the　S-CO2　coal-fired　power　system　with　the　inter-cooling　cycle　yields　highest　efficiency　and　is　the　most　economic　configuration.　The　thermal　efficiency　of　the　S-CO2　coal-fired　power　plant　composing　the　inter-cooling　cycle　is　47.69–49.09%　with　total　thermal　conductance　of　recuperators　changed　from　120　MW·K−1　to　180　MW·K−1　when　the　turbine　inlet　parameters　are　620　°C/620　°C/30　MPa,　and　displays　an　advantage　over　the　ultra-supercritical　steam　Rankine　power　plant.　The　system　levelized　cost　of　electricity　is　0.0397　$·(kW·h)−1　and　shows　great　commercial　potential.　The　detailed　discussion　of　this　study　is　beneficial　to　a　comprehensive　understanding　of　various　S-CO2　coal-fired　power　systems　and　provide　a　clue　to　establish　a　practical　power　plant　for　the　application　of　coal-fired　industry.　©　2020　Elsevier　Ltd