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BACKGROUND Coronavirus disease 2019 (COVID‐19) and cancer are serious public health problems worldwide. However, little is known about the risk factors of in‐hospital mortality among COVID‐19 patients with and without cancer in Brazil. The objective of this study was to evaluate the risk factors of in‐hospital mortality among COVID‐19 patients with and without cancer and to compare mortality according to gender and topography during the year 2020 in Brazil. METHODS This was a secondary data study of hospitalized adult patients with a diagnosis of COVID‐19 by real‐time polymerase chain reaction testing in Brazil. The data were collected from the Influenza Epidemiological Surveillance Information System. RESULTS This study analyzed data from 322,817 patients. The prevalence of cancer in patients with COVID‐19 was 2.3%. COVID‐19 patients with neurological diseases and cancer had the most lethal comorbidities in both sexes. COVID‐19 patients with cancer were more likely to be older (median age, 67 vs 62 years; P < .001), to have a longer hospital stay (13.1 vs 11.5 days; P < .001), to be admitted to the intensive care unit (45.3% vs 39.6%; P < .001), to receive more invasive mechanical ventilation (27.1% vs 21.9%), and to have a higher risk of death (adjusted odds ratio [aOR], 1.94; 95% confidence interval [CI], 1.83‐2.06; P < .001) than those without cancer. Patients with hematological neoplasia (aOR, 2.85; 95% CI, 2.41‐3.38; P < .001) had a higher risk of mortality than those with solid tumors (aOR, 1.83; 95% CI, 1.72‐1.95; P < .001) in both sexes. CONCLUSIONS Brazilian COVID‐19 patients with cancer have higher disease severity and a higher risk of mortality than those without cancer., Patients with hematological neoplasia (adjusted odds ratio [aOR], 2.85; 95% confidence interval [CI], 2.41‐3.38; P < .001) have a higher risk of mortality than those with solid tumors (aOR, 1.83; 95% CI, 1.72‐1.95; P < .001) in both sexes.