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Abstract Background Salinity stress is a major limiting factor for plant growth, particularly in arid and semi-arid environments. To mitigate the detrimental effects of salinity stress on vegetable production, selenium (Se) biofortification and grafting onto tolerant rootstocks have emerged as effective and sustainable cultivation practices. This study aimed to investigate the combined effects of Se biofortification and grafting onto tolerant rootstock on the yield of cucumber grown under salinity stress greenhouse conditions. The experiment followed a completely randomized factorial design with three factors: salinity level (0, 50, and 100 mM of NaCl), foliar Se application (0, 5, and 10 mg L-1 of sodium selenate) and grafting (grafted and non-grafted plants) using pumpkin (Cucurbita maxima) as the rootstock. Each treatment was triplicated. Results The results of this study showed that Se biofortification and grafting significantly enhanced salinity tolerance in grafted cucumbers, leading to increased yield and growth. Moreover, under salinity stress conditions, Se-Biofortified plants exhibited increased leaf relative water content (RWC), proline, total soluble sugars, protein, phenol, flavonoids, and antioxidant enzymes. These findings indicate that Se contributes to the stabilization of cucumber cell membrane and the reduction of ion leakage by promoting the synthesis of protective compounds and enhancing antioxidant enzyme activity. Moreover, grafting onto pumpkin resulted in increased salinity tolerance of cucumber through reduced Na uptake and translocation to the scion. Conclusion In conclusion, the results highlight the effectiveness of Se biofortification and grafting onto pumpkin in improving cucumber salinity tolerance. A sodium selenate concentration of 10 mg L-1 is suggested to enhance the salinity tolerance of grafted cucumbers. These findings provide valuable insights for the development of sustainable cultivation practices to mitigate the adverse imp