The 78-year-old head of the Roman Catholic Church is under pressure to use the term publicly to describe the Ottoman Turk murders, but will be wary of alienating an important ally in the fight against radical Islam.
While many historians describe the cull as the 20th century's first genocide, Turkey hotly denies the accusation.
Francis and Armenian patriarch Nerses Bedros XIX Tarmouni will celebrate a mass in Saint Peter's Basilica, which will include elements of the Armenian Catholic rite and be attended by the country's President Serzh Sargsyan.
The mass, which begins at 0700 GMT, is being held ahead of the official April 24 commemoration of the murders.
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Armenians say up to 1.5 million of their kin were killed between 1915 and 1917 as the Ottoman Empire was falling apart, and have long sought to win international recognition of the massacres as genocide.
But Turkey rejects the claims, arguing that 300,000 to 500,000 Armenians and as many Turks died in civil strife when Armenians rose up against their Ottoman rulers and sided with invading Russian troops.
Using the word would not be a papal first: John Paul II used it in a joint statement signed with the Armenian patriarch in 2000 which said "the Armenian genocide, which began the century, was a prologue to horrors that would follow".
But it provoked outrage in Turkey, and a year later during a trip to Armenia the pontiff avoided using the term, instead opting for "Metz Yeghern", an expression meaning "Great Evil", used by Armenians to describe the killings.