Diverse plant products (e.g. fruits, vegetables, legumes) are associated with decreased cancer risk at several locations while red and processed meat were found to increase cancer risk. A pro plant-based dietary score reflecting the relative contribution of consumed plant vs animal products was developed, and was associated with lower overall mortality, type 2 diabetes and cardiovascular disease risk, among omnivorous adults. For the first time, we investigated the prospective associations between this pro plant-based dietary score and cancer risk. This study included 42,544 men and women of the French NutriNet-Santé prospective cohort (2009-2016) aged ≥45 years who completed at least three 24-hr-dietary records during the first year of follow-up. The risk of developing cancer was compared across sex-specific tertiles of pro plant-based dietary score by multivariable Cox models. In total, 1,591 first primary incident cancer cases were diagnosed during follow-up, among which 487 breast, 243 prostate, 198 digestive and 68 lung cancers. A higher pro plant-based dietary score was associated with decreased risks of overall (HR =0.85; 95% CI 0.76, 0.97; P =0.02), digestive (HR =0.68; 95% CI 0.47; 0.99; P = 0.04) and lung (HR =0.47; 95% CI 0.25, 0.90; P =0.02) cancer, though no substantial associations were found for breast or prostate cancers. This large cohort study supports a beneficial role of higher intakes of plant-based products along with lower intakes of animal products, within a balanced omnivorous diet, regarding primary cancer prevention. These results are consistent with mechanistic evidence from experimental studies.