Background:　There　is　limited　research　on　cholesterol　metabolism-related　genes　(CM-RGs)　in　non-alcoholic　fatty　liver　disease　(NAFLD),　despite　hypercholesterolemia　being　a　recognized　risk　factor.　The　role　of　CM-RGs　in　NAFLD　remains　unclear.　Methods:　The　differentially　expressed　genes　(DEGs)　between　NAFLD　and　control　were　acquired　by　differential　expression　analysis.　The　differentially　expressed　genes　associated　with　cholesterol　metabolism　(DE-CM-RGs)　were　identified　and　functional　enrichment　analyses　were　performed.　Protein-protein　interaction　network　analysis　and　a　two-sample　Mendelian　randomization　study　were　utilized　for　identifying　hub　genes.　Nomogram　model,　competing　endogenous　RNA　and　messenger　RNA-drug　networks　were　established.　In　addition,　immunoinfiltration　analysis　was　performed.　Results:　We　identified　four　hub　genes　(MVK,　HMGCS1,　TM7SF2,　and　FDPS)　linked　to　NAFLD　risk.　MVK　and　TM7SF2　were　protective　factors,　HMGCS1　and　FDPS　were　risk　factors　for　NAFLD.　The　area　under　the　curve　values　of　nomograms　in　GSE135251　and　GSE126848　were　0.79　and　0.848,　respectively.　The　gene　set　enrichment　analysis　indicated　that　hub　genes　participated　in　calcium　signaling　pathways　and　biosynthesis　of　unsaturated　fatty　acids.　NAFLD　patients　showed　increased　CD56dim　NK　cells　and　Th17.　Tretinoin,　alendronate,　zoledronic　acid,　and　quercetin　are　potential　target　agents　in　NAFLD.　Conclusion:　Our　study　has　linked　cholesterol　metabolism　genes　(MVK,　HMGCS1,　TM7SF2,　and　FDPS)　to　NAFLD,　providing　a　promising　diagnostic　framework,　identifying　treatment　targets,　and　offering　novel　perspectives　into　its　mechanisms.　Copyright　©　2024　Chen,　Rao　and　Zheng.