ABSTRACT: The incidence of early-onset colorectal cancer, defined as colorectal cancer occurring in young adults under the age of 50, is increasing globally. Knowledge of the etiological factors in young adults is far from complete. Questionable eoCRCs' exogenous factors are represented by processed meat, sugary drinks, alcohol, Western dietary pattern, overweight and obesity, physical inactivity, and smoking, though with heterogeneous results. Therefore, we performed a systematic review to summarize the current evidence on the role of diet and lifestyle as eoCRC risk factors. We systematically searched PubMed, Scopus, and EMBASE up to July 2021, for original studies evaluating diet, alcohol, physical activity, BMI, and smoking in eoCRC and included twenty-six studies. Indeed, the exogenous factors could represent modifiable key factors, whose recognition could establish areas of future interventions through public health strategies for eoCRC primary prevention. Additionally, we discussed the role of additional non-modifiable risk factors, and of epigenetic regulation and microbiota as mediators of the eoCRC triggered by diet and lifestyle.