Objective: To analyze the trend of standardized cancer mortality rate in the state of Mato Grosso according to health regions, from 2000 to 2015. Methods: Ecological time series study with data on deaths by cancer from the Mortality Information System. The rates were standardized using direct method and calculated by year and health regions. The annual percentage changes (APC) and respective confidence interval (95%CI) were obtained through simple linear regression. Thematic maps were built to show the spatial distribution of rates. Results: There were 28,525 deaths by cancer registered in Mato Grosso, with the main types being lung, prostate, stomach, breast and liver cancer. The highest mortality rates were found in regions Médio Norte, Baixada Cuiabana and Sul Mato-Grossense. From 2000 to 2015, an upward trend was seen in the mortality rate by cancer in Mato Grosso (APC=0.81%; 95%CI 0.38–1.26), and in four health regions, Garças Araguaia (APC=2.27%; 95%CI 1.46–3.08), Sul Mato-Grossense (APC=1.12%; 95%CI 0.28–1.97), Teles Pires (APC=1.93%; 95%CI 0,11–3,74) and Vale dos Arinos (APC=2.61%; 95%CI 1.10–4.70), while the other regions remained stable. Conclusion: In the state of Mato Grosso and in the four health regions, cancer mortality rate showed a growing trend. The results point to the need to consider regional differences when thinking about actions for cancer prevention, control and assistance.