Background:　Both　alcohol　misuse　and　sleep　deficiency　are　associated　with　deficits　in　semantic　processing.　However,　alcohol　misuse　and　sleep　deficiency　are　frequently　comorbid　and　their　inter-related　effects　on　semantic　processing　as　well　as　the　underlying　neural　mechanisms　remain　to　be　investigated.　Methods:　We　curated　the　Human　Connectome　Project　data　of　973　young　adults　(508　women)　to　examine　the　neural　correlates　of　semantic　processing　in　link　with　the　severity　of　alcohol　use　and　sleep　deficiency.　The　latter　were　each　evaluated　using　the　first　principal　component　(PC1)　of　principal　component　analysis　of　all　drinking　metrics　and　the　Pittsburgh　Sleep　Quality　Index　(PSQI).　We　employed　path　modeling　to　elucidate　the　interplay　among　clinical,　behavioral,　and　neural　variables.　Results:　Among　women,　we　observed　a　significant　negative　correlation　between　the　left　precentral　gyrus　(PCG)　and　PSQI　scores.　Mediation　analysis　revealed　that　the　left　PCG　activity　fully　mediated　the　relationship　between　PSQI　scores　and　word　comprehension　in　language　tasks.　In　women　alone　also,　the　right　middle　frontal　gyrus　(MFG)　exhibited　a　significant　negative　correlation　with　PC1.　The　best　path　model　illustrated　the　associations　among　PC1,　PSQI　scores,　PCG　activity,　and　MFG　activation　during　semantic　processing　in　women.　Conclusions:　Alcohol　misuse　may　lead　to　reduced　MFG　activation　while　sleep　deficiency　hinder　semantic　processing　by　suppressing　PCG　activity　in　women.　The　pathway　model　underscores　the　influence　of　sleep　quality　and　alcohol　consumption　severity　on　semantic　processing　in　women,　suggesting　that　sex　differences　in　these　effects　need　to　be　further　investigated.