ABSTRACT: BACKGROUND:Evidence is suggestive of sedentary behaviour being associated with an increased risk of endometrial cancer, but the evidence base is too limited to draw any conclusions for other cancers. The aim of the study was to investigate the association between recreational screen time and site-specific cancer risk. METHODS:We analysed data from the prospective UK Biobank cohort study. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between daily recreational screen time (including television (TV) viewing time, computer use time and total screen time) and site-specific cancer risk. Partition models and isotemporal substitution models investigated the impact of substituting recreational screen time with physical activity. RESULTS:During a mean follow-up of 7.6?years, 28,992 incident cancers were identified among 470,578 adults. A 1-h increase in daily TV viewing time was associated with higher risks of oropharyngeal, oesophago-gastric and colon cancer in fully adjusted models. Participants who reported ?1, compared with 1-???3, hours/day of TV viewing time had lower risks of lung, breast, and oesophago-gastric cancer. Findings were inconsistent for daily recreational computer use and daily total recreational screen time. The majority of observed associations were small, and were attenuated after excluding cancers diagnosed within the first two years of follow-up, except for oesophago-gastric and colon cancers (HR 1.05, 95% CI: 1.01, 1.10; and HR 1.04, 95% CI: 1.01, 1.07 per 1-h increase in daily TV viewing time, respectively). However, isotemporal substitution models showed reduced risk of some site-specific (oropharyngeal, lung, breast and colorectal) cancers when replacing 1-h/day of TV viewing with 1-h of moderate-intensity physical activity or walking. CONCLUSIONS:Our findings show that daily recreational screen time, particularly TV viewing, was associated with small increased risks of oesophago-gastric and colon cancer. Replacing 1-h/day of TV viewing with 1-h of moderate-intensity physical activity or walking was associated with lower risk of oropharyngeal, lung, breast and colorectal cancers. Further research from other large prospective cohort studies is required, while mechanistic research is warranted to enhance the biological plausibility of these findings.