Background　GI　cancers　pose　an　increasing　global　health　burden,　with　their　impact　on　the　working-age　population　(WAP)　aged　15-64　years　remaining　largely　unexplored　despite　the　crucial　role　of　this　group　in　societal　and　economic　well-being.　Objective　To　assess　trends　and　cross-country　inequality　in　the　global　burden　of　six　GI　cancers　from　1990　to　2021　among　individuals　in　the　WAP.　Design　The　2021　Global　Burden　of　Disease　study　dataset　was　used　to　obtain　estimates　of　GI　cancer　incidence　and　95%　uncertainty　intervals,　including　the　number　of　cases,　crude　incidence　rate　and　age-standardised　incidence　rate　(ASIR).　WAP　GI　cancer　epidemiology　was　assessed　at　the　national,　regional　and　global　levels,　evaluating　trends　from　1990　to　2021　from　overall,　local　and　Sociodemographic　Index　(SDI)　perspectives　and　using　standard　health　equity　methods　to　quantify　cross-country　inequality.　Results　Colorectal　cancer　exhibited　the　greatest　burden　of　GI　cancer　among　the　WAP　in　2021.　From　1990　to　2021,　the　number　of　GI　cancer　cases　rose　by　51.9%,　although　the　ASIR　declined　by　23.4%.　These　rates　exhibit　geographic　variation,　with　the　most　cases　and　the　highest　ASIR　in　China　and　Mongolia,　respectively.　Incidence　was　disproportionately　concentrated　in　higher　SDI　countries,　and　worsening　inequality　was　evident　over　time.　Conclusions　While　the　ASIR　of　GI　cancer　is　trending　downwards　among　the　WAP,　high　incidence　rates,　regional　variability　and　an　unequal　burden　of　disease　emphasise　the　need　for　flexible,　targeted　medical　interventions　to　support　policymaking　and　medical　resource　allocation.　　©　Author(s)　(or　their　employer(s))　2025.