Abstract This study aimed to analyze the role of period, geographic and socio demographic factors in cancer-related mortality by prostate, breast, cervix, colon, lung and esophagus cancer in Brazilians capitals (2000-2015). Ecological study using data of Brazilian Mortality Information. Multilevel Poisson models were used to estimate the adjusted risk of cancer mortality. Mortality rate levels were higher in males for colon, lung and esophageal cancers. Mortality rates were highest in the older. Our results showed an increased risk of colon cancer mortality in both sexes from 2000 to 2015, which was also evidenced for breast and lung cancers in women. In both genders, the highest mortality risk for lung and esophageal cancers was observed in Southern capitals. Midwestern, Southern and Southeastern capitals showed the highest mortality risk for colon cancer both for males and females. Colon cancer mortality rate increased for both genders, while breast and lung cancers mortality increased only for women. The North region showed the lowest mortality rate for breast, cervical, colon and esophageal cancers. The Midwest and Northeast regions showed the highest mortality rates for prostate cancer.