Introduction: Patients diagnosed with end-stage chronic kidney disease on a hemodialysis program (HDP) represent a risk group for COVID-19. Scientific societies have developed guidelines for the prevention of contagion, but there is no prophylactic medicine in them. Objectives: To describe the safety and efficacy of recombinant intranasal human Interferon alfa 2b as prophylaxis for COVID-19 in patients in an HDP. Patients and Methods: Intervention description through the monitoring of 15 patients in outpatient HDP. Prior to the administration of the drug, clinical, radiological evaluation and hematology and blood chemistry studies were performed. Daily contact was made with each study patient in person or by telephone, asking about the occurrence of adverse events or symptoms of disease. Results: In 47% of the patients, there was leukopenia, lymphopenia in 67% and anemia and thrombocytopenia in 33% respectively, prior to the use of the drug. There was no clinical suspicion of COVID-19 in any of them. Adverse events occurred in 3 patients (20%), all were mild and non-severe. All patients were negative for SARS-CoV-2 real-time polymerase chain reaction (rtPCR) and antibody studies 45 days after the study started. Conclusion: the use of intranasal recombinant human interferon alfa 2b as prophylaxis of COVID-19 in patients in a HDP at a dose of 1 MIU daily for ten days, as part of a prevention protocol, has an adequate safety profile. None of the patients in the series was infected with SARS-CoV-2 during the surveillance period.