Horner said it was "unfair" to boo Vettel, who has suffered repeated ill-treatment this year and was again subjected to loud chants and heckles after winning Sunday's Singapore Grand Prix.
The 26-year-old star did his best to shrug off the jeers but Horner said the booing, blamed on a particular group of fans, might be getting under his skin.
"There is a small collective group and it is like a pantomime, but it is so unfair because it is not sporting," said Horner, according to Autosport.Com.
"He is a great kid. He has a great sense of humour. He has a big heart at the end of the day."
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Booing erupted after Vettel's wins in Belgium and Italy, and surprisingly at the less partisan circuit of Singapore, as Vettel moved closer to a fourth straight world title.
On Sunday night, he led from pole position to the chequered flag in an astounding, if not terribly viewer-friendly, demonstration of uncatchable front-running.
But there is also residual anger after Vettel controversially ignored team orders and passed team-mate Mark Webber to win the Malaysian Grand Prix in March.
While Vettel apologised to Webber at the time, he later struck a defiant tone and insisted he would do the same again. Webber has announced his departure from the team at the end of the season.