BackgroundResearch on glucosamine shows anti-inflammatory and anti-cancer benefits with a minimal adverse effects. We aimed to explore the relationship between use of glucosamine and risk of lung cancer and lung cancer mortality based on data from the large-scale nationwide prospective UK Biobank cohort study.MethodsParticipants were enrolled between the year 2006 and 2010 and followed up to 2020. Cox proportion hazards model were used to assess the relationship between glucosamine use and risk of lung cancer and lung cancer mortality. Subgroup analyses and sensitivity analyses were performed to explore the potential effect modifications and the robustness of main findings.ResultsA total of 439,393 participants (mean age: 56 years; 53% females) with a mean follow-up of 11 years were included for analyses. There were 82,603 (18.80%) participants reporting regular use of glucosamine at baseline. During follow-up, there were 1,971 (0.45%) lung cancer events documented. Glucosamine use was significantly associated with a decreased risk of lung cancer (hazard ratio=0.84, 95% CI: 0.75–0.92, p<0.001) and lung cancer mortality (hazard ratio=0.88, 95% CI: 0.81–0.96, p=0.002) in fully-adjusted models. A stronger association between glucosamine use and decreased lung cancer risk was observed in participants with a family history of lung cancer when compared to those without a family history.ConclusionRegular use of glucosamine was significantly related with decreased risk of lung cancer and lung cancer mortality, based on data from this nationwide prospective cohort study.