The Spaniard, who was appointed as Pep Guardiola's successor at Camp Nou in June 2012, was diagnosed with the disease in November the previous year.
He later had a tumour removed from his parotid gland and underwent chemotherapy and radiotherapy treatment for around six weeks, but eventually was forced to step down from his managerial role last summer after he relapsed.
The Catalan giants wrote on their official Twitter page: "The FC Barcelona is in immense mourning. Tito Vilanova has died at the age of 45. May he rest in peace."
Vilanova began his football career in the Barcelona youth team and went on to play for clubs including Mallorca and Elche, before moving into coaching and management.