In recent years, morbidity and mortality due to cancer has been increasing in Ethiopia, putting it among the most important public health issues. Cancer and associated complications can be prevented provided that effective interventions are put in place to control risk factors. Therefore, this study aimed to assess the level of knowledge and practice of preventable behavioural risk factors of cancer. We conducted a cross-sectional study among 200 college students in Northeast Ethiopia utilising quantitative methods of data collection. Data on socioeconomic characteristics, health belief variables, knowledge and behavioural risk factors (alcohol consumption, tobacco smoking, physical activity and dietary practice) were collected. The level of knowledge and practice was summarised using descriptive statistics. To investigate the variation in knowledge and practice across sociodemographic characteristics, we performed Pearson Chi-square test or Fisher’s exact test. The majority (81.0%) of participants was male and 82.0% were in the age group of 18–24 years. More than half (61.0%) of them had poor knowledge about the behavioural risk factors of cancer. Nearly one-third (30.5%) consume alcohol, whereas 16.0%, 18.0% and 20.0%, respectively, smoke tobacco, consume street food and packed-fried snacks daily. Alcohol consumption (p = 0.02) and level of vigorous physical activity (p = 0.001) were significantly higher among males than females. Alcohol consumption, tobacco smoking and unhealthy dietary practice were remarkably high, whereas knowledge towards the behavioural risk factors was low. Therefore, health education and collaborative action between different sectors are needed to counter the emerging problem.