Among cancers, colorectal cancer is the third most common cancer in the world and the fourth leading cause of cancer deaths worldwide. Some studies have shown that the incidence of colorectal cancer is increasing in Iran and in Fars province. The present study aimed to determine the economic burden of colorectal cancer in patients referred to the referral centers affiliated to Iran, Shiraz University of Medical Sciences in 2019 from the patients’ perspective. This is a partial economic evaluation and a cost-of-illness study conducted cross-sectionally in 2019. All the patients with colorectal cancer who had been referred to the referral centers affiliated to Iran, Shiraz University of Medical Sciences, and had medical records were studied through the census method (N = 96). A researcher-made data collection form was used to collect the cost data. The prevalence-based and bottom-up approaches were also used in this study. The human capital approach was applied to calculate indirect costs. The mean annual cost per patient with colorectal cancer in the present study was $10930.98 purchasing power parity (PPP) (equivalent to 5745.29 USD), the main part of which was the medical direct costs (74.86%). Also, among the medical direct costs per patient, the highest were those of surgeries (41.7%). In addition, the mean annual cost per patient with colorectal cancer in the country was $ 116917762 PPP (equivalent to 61451621.84 USD) in 2019. Regarding the considerable economic burden of colorectal cancer and in order to reduce the costs, these suggestions can be made: increasing the number of specialized beds through the cooperation of health donors, establishing free or low-cost accommodation centers for patients and their companions near the medical centers, using the Internet and cyberspace technologies to follow up the treatment of patients, and increasing insurance coverage and government drug subsidies on drug purchase.