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Background: It remains unclear if choline intake is associated with colorectal cancer. Therefore, we examined data from the National Health and Nutrition Examination Survey (NHANES)., Methods: This cross-sectional study included 32,222 U.S. adults in the 2005-2018 NHANE cycles, among whom 227 reported colorectal cancer. Dietary choline was derived from 24-h recalls. Logistic regression estimated odds of colorectal cancer across increasing intake levels, adjusting for potential confounders., Results: After adjusting for sociodemographic variables, BMI, alcohol use, smoking status, comorbidities, and dietary factors (energy, fat, fiber, and cholesterol), the odds ratio (OR) for colorectal cancer was 0.86 (95% CI: 0.69-1.06, p  = 0.162) per 100 mg higher choline intake. Across increasing quartiles of choline intake, a non-significant inverse trend was observed (Q4 vs. Q1 OR: 0.76, 95%CI: 0.37 ~ 1.55, P -trend = 0.23). Subgroup analyses revealed largely consistent associations, with a significant interaction by hypertension status ( P -interaction =0.022)., Conclusion: In this large, nationally representative sample of U.S. adults, higher dietary choline intake was not significantly associated with colorectal cancer odds after adjusting for potential confounders. However, a non-significant inverse trend was observed. Further prospective studies are needed to confirm these findings and elucidate the underlying mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Xu, Ying, Huang, Hong and Chen.)