Background: The incidence of early-onset colorectal cancer (EO-CRC), colorectal cancer (CRC) diagnosed in individuals younger than 50 years, is rapidly increasing in the United States. However, risk factors for EO-CRC are poorly understood. Identifying potential risk factors using population-based health data is critical to identify at-risk populations and develop cost-effective screening guidelines and other prevention strategies. This study aimed to identify potential modifiable and non-modifiable risk factors associated with EO-CRC. Methods: This cross-sectional study used data from 2004-2018 National Health Interview Survey (NHIS), a nationally representative health information of US population collected through personal household interviews. Individuals who were at an age of 18-49 years and had a history of CRC diagnosis at the time of the interview were identified as patients with EO-CRC, and their demographic, clinical, and behavioral characteristics were compared with those of non-cancer young adult (18-49 years) population. In addition, their non-age-related characteristics (gender, race/ethnicity, region, and body mass index [BMI]) were compared with those of individuals who were diagnosed with CRC at age 50 or older (late-onset CRC; LO-CRC). For both comparisons, bivariate and multivariable logistic regression (proc surveylogistic) analyses were performed. Results: We identified 156 patients with EO-CRC (weighted: 105,300; 46.4% female; mean age = 41.8 [SE = 0.69]), 204,846 with non-cancer (weighted: 126,257,662; 50.7% female; mean age = 33.6 [SE = 0.05]), and 1,972 with LO-CRC (weighted: 920,231; 48.6% female; mean age = 72.6 [SE = 0.28]). Results from the comparison between patients with EO-CRC and non-cancer population showed that higher odds of having EO-CRC were associated with older age (Odds Ratio [OR] = 1.11; 95% CI = 1.08–1.14), living in Midwest (vs. South; OR = 1.64, 95% CI = 1.06 – 2.55), and history of alcohol consumption (vs. lifetime abstainer; OR = 2.09, 95% CI = 1.01 – 4.36). Lower odds of having EO-CRC were associated with being Hispanic or Asian (vs. non-Hispanic White; OR = 0.43, 95% CI = 0.22 – 0.84 and OR = 0.38, 95% CI = 0.16 – 0.92, respectively) and doing vigorous physical activity (vs. no activity; OR = 0.34; 95% CI = 0.21 – 0.55). Gender, BMI, diabetes, and smoking were not significantly different between the two groups. Compared with patients with LO-CRC, those with EO-CRC were more likely to be Hispanic (vs. non-Hispanic White; OR = 2.21, 95% CI = 1.14 – 4.31) and live in Midwest (vs. South; OR = 1.62, 95% CI = 1.02 – 2.58). Gender and BMI were not significantly different between the two groups. Conclusions: In this cross-sectional population-based study, we identified potential modifiable (alcohol consumption and physical activity) and non-modifiable (age, race/ethnicity, and region) risk factors associated with EO-CRC.