The "The Radio Factor" - which began in 2002 and runs on more than 400 radio stations, as well as satellite operator Sirius XM Radio Inc. - will end in the first quarter of 2009, Fox said.
In a statement, O'Reilly said the workload has become too much, adding, "I can no longer give both TV and radio the time they deserve."
O'Reilly will continue hosting "The O'Reilly Factor" on the Fox News Channel and writing his weekly newspaper column.
Fox News is a unit of News Corp.
