Ajmal, who turns 36 on the first day of the match, took 24 wickets when Pakistan humbled then world number one England 3-0 in the United Arab Emirates last year.
But Misbah urged his wily spinner to lift his game.
"I think it (bowling to South Africans) will be a big challenge for Ajmal," said Misbah at the unveiling of the trophy for the series.
Misbah conceded South Africans play Ajmal better than English batsmen.
"He (Ajmal) was new to England and that's why they struggled against him. South Africans have played him more, so it's a big challenge for Ajmal and he will have to lift his bowling because he is up against a team who plays him well," said Misbah.
Smith agreed his batsmen play Ajmal well, but the off-spinner can still pose a challenge.
"I think last time we were on this tour, we played Ajmal really well and I think he ended up missing a few games on the tour," said Smith of South Africa's last series here in 2010 when Ajmal was dropped after taking only three wickets in the first Test.
"He still is a key performer for Pakistan and he's a world class performer... It's real respect factor for what he can do... He's a world class bowler, I think we've had a good success against him and that's nice to know," said Smith, who returns to international cricket after a 21-week break following an ankle operation.
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