De Mistura invoked the genocides in Rwanda in 1994 and in the Bosnian town of Srebrenica in July 1995 as he appealed to the world to prevent another catastrophe.
If the town falls to the Islamic State fighters, "we know what they are capable of doing," said the Italian-Swedish diplomat, who was appointed to the U.N. post in July.
The civilians of Kobani "will be most likely massacred," de Mistura said. "When there is an imminent threat to civilians, we cannot, we should not be silent."
"You remember Srebrenica? We do. We never forgot. And probably we never forgave ourselves for that," he said. In both Rwanda and Srebrenica, the U.N. had troops on the ground but they failed to save the lives of the civilians they were mandated to protect.
There are no U.N. troops in Syria. Turkey has deployed troops and tanks across the border, but despite U.S. pressure, Ankara has said it will not join the fight unless the U.S.-led coalition also goes after the government of Syrian President Bashar Assad.
De Mistura appealed to Turkish authorities to allow volunteers and equipment to flow into Kobani and help its Syrian Kurdish defenders.
Without more such help, he added, Kobani is "likely to fall."
The fight over Kobani has eclipsed the larger Syrian civil war, where Assad’s forces continue to fight rebels seeking to topple him in many parts of the country.
On Friday, activists said at least nine civilians were killed in a government airstrike that targeted the village of Harra in the southern province of Daraa. More than 20 people were also killed a day earlier in government airstrikes in Damascus suburbs, they said.
The Syrian National Coalition, Syria’s Western-backed main opposition group, accused Assad of "openly exploiting" the coalition’s war against the Islamic State group to continue killing Syrians.