He would back an accord, but only if neither side got everything it wanted, he said in a statement.
The comments came as the US and Iran held further talks in Munich.
Iran and six international powers are aiming to reach a framework agreement in March and a final deal by 30 June.
The world powers want Iran to curb its nuclear programme in return for the lifting of sanctions.
Ayatollah Khamenei said he backed President Hassan Rouhani’s line that “negotiations are all about trying to reach a common stand”.
This meant that no side could end up getting everything it wanted, he said, warning that “it’s better to have no deal than one that goes against our national interests”.
He also expressed reservations about the current plan of reaching an agreement in two stages, first on general issues and then on details.
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