Background: Similar to many countries, Belgium experienced a rapid increase in cancer diagnoses in the last years. Considering that a large part of cancer types could be prevented, our study aimed to estimate the annual healthcare burden of cancer per site, and to compare cost with burden of disease estimates to have a better understanding of the impact of different cancer sites in Belgium. Methods: We used nationally available data sources to estimate the healthcare expenditure. We opted for a prevalence-based approach which measures the disease attributable costs that occur concurrently for 10-year prevalent cancer cases in 2018. Average attributable costs of cancer were computed via matching of cases (patients with cancer by site) and controls (patients without cancer). Years of life lost due to disability (YLD) were used to summarize the health impact of the selected cancers. Results: The highest attributable cost in 2018 among the selected cancers was on average €15,867 per patient for bronchus and lung cancer, followed by liver cancer, pancreatic cancer, and mesothelioma. For the total cost, lung cancer was the most costly cancer site with almost €700 million spent in 2018. Lung cancer was followed by breast and colorectal cancer that costed more than €300 million each in 2018. Conclusions: In our study, the direct attributable cost of the most prevalent cancer sites in Belgium was estimated to provide useful guidance for cost containment policies. Many of these cancers could be prevented by tackling risk factors such as smoking, obesity, and environmental stressors.