Abstract Several national and international authorities have proposed nutritional and lifestyle recommendations with the aim of improving health of the general population. Scores of adherence to these recommendations can be calculated at the individual level. Here, we investigated the associations between four nutritional scores and overall, breast, prostate, and colorectal cancer risk in a large prospective population-based cohort: the cancer-specific World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) score, the Alternate Healthy Eating Index 2010 (AHEI-2010), a score based on adherence to the Mediterranean diet (MEDI-LITE), and the French National Nutrition Health Program-Guideline Score (PNNS-GS). This study included 41,543 participants aged ≥40 years from the NutriNet-Santé cohort (2009–2017). A total of 1,489 overall incident cancers were diagnosed. A one-point increment of the WCRF/AICR score was significantly associated with decreased overall [12%; 95% confidence interval (CI), 8%–16%; P < 0.0001], breast (14%; 95% CI, 6%–21%; P = 0.001), and prostate (12%; 95% CI, 0%–22%; P = 0.05) cancer risks. Hazard ratio for colorectal cancer risk was 0.86 (95% CI, 0.72–1.03; P = 0.09). The PNNS-GS score was associated with reduced colorectal cancer risk (P = 0.04) and AHEI-2010 was associated with reduced overall cancer risk (P = 0.03). The WCRF/AICR score performed best. Compared with other tested scores, it included a stronger penalty for alcohol, which is a major risk factor for several cancer sites. Better adherence to nutritional recommendations, especially those designed for cancer prevention, could substantially contribute to decreased cancer incidence. Significance: This large prospective population-based cohort study suggests that following dietary recommendations such as the ones proposed by the World Cancer Research Fund/American Institute for Cancer Research could significantly contribute to cancer prevention. Cancer Res; 78(15); 4427–35. ©2018 AACR.