OBJECTIVES: To identify risk factors and examine associations between colorectal cancer (CRC) status and modifiable and non-modifiable risk factors among patients diagnosed in Oman, considering the existence and increase of incidence and prevalence of these risk factors. DESIGN: A multicentre case-control study. SETTING: Sultan Qaboos University Hospital and the Royal Hospital in Muscat, Oman. PARTICIPANTS: Patients diagnosed with CRC (n=166) and controls (n=166). OUTCOME MEASURES: A questionnaire adapted from the Colon Cancer Family Registry and other previously published studies was used to collect data on sociodemographic characteristics, modifiable and non-modifiable CRC risk factors and coexisting morbidities. Univariable and multivariable logistic regression analyses were performed to examine associations between CRC status and independent variables. RESULTS: Multivariable analysis demonstrated significant associations between CRC status and several risk factors. Smoking was associated with a fourfold increased risk of CRC (adjusted OR (aOR): 4.35, 95% CI 2.26 to 8.36). Higher body mass index was also associated with increased CRC risk (aOR: 2.42, 95% CI 1.23 to 4.76), while individuals with a family history of CRC, including first-degree relatives (biological parents, siblings and children) and second-degree relatives (grandparents, uncles and aunts) had more than double the risk (aOR: 2.10, 95% CI 1.15 to 3.82). Also, polyps had double the risk (aOR 2.61, 95% CI 1.40 to 4.84) In addition, CRC was more common among patients with diabetes (aOR 2.70, 95% CI 1.52 to 4.80), hypertension (aOR 4.13, 95% CI 2.03 to 8.42) and inflammatory bowel disease (aOR 3.48, 95% CI 1.13 to 10.67). CONCLUSIONS: Considering the existence of non-modifiable risk factors and the increase in incidence and prevalence of modifiable risk factors of CRC in Oman, the findings of this study underscore the need for targeted awareness initiatives, risk-based screening and early surveillance, particularly among high-risk groups. The results also support integrating smoking cessation, weight management and optimal control of chronic diseases into national CRC prevention programmes to reduce the overall CRC disease burden.