Objective. To estimate the disease burden of cancer in theaffiliate population of the Mexican Social Security Institute (Instituto Mexicano del Seguro Social, IMSS) in 2010 by delegation. Materials and methods. The Disability-Adjusted Life Years (DALYs), Years of Life Lost (YLL) due to premature mortality and Years Lived with Disability/Disease (YLD) for 21 specific cancers and a subgroup of other malignant neoplasms were calculated based on the methodology of the Global Burden of Disease Study (GBD) for each of the 35 delegations of the IMSS. Results. In 2010, cancer represented the fifth overall leading cause of disease burden in IMSS affiliates (16.72 DALYs/1000 affiliates). A total of 75% of the cancer disease burden in each delegation is due to ten specific cancers, particularly breast cancer, which ranks first in 82% of the delegations. Prostate cancer; tracheal, bronchial, and lung cancers; leukemia, and colorectal and stomach cancers occupy the second to fourth positions in each delegation. With the exception of breast and prostate cancer, for which the contribution of YLD to the DALYs was higher than 50%, the greatest contribution to the DALYs of the other cancers was premature mortality, which accounted for more than 90% of the DALYs in some cases. Conclusion. The results obtained in this study allow for the identification of intervention priorities with regard to cancer at the institutional level and also for the focus at the delegation level to be placed on cancers ranking in the top positions for disease burden.