The Material Girl was performing at the Staples Center in Los Angeles as part of her MDNA tour when she gave an onstage shout-out to the young education-activist who was shot on her way home from school in Mingora, Pakistan, last week.
"This made me cry," Madonna said to the 18,000 fans in attendance. "The 14-year-old Pakistani girl who was shot on a school bus for writing a blog... Who wrote a blog about how important education was to her. The Taliban stopped her bus and shot her... Do you understand the sickness and absurdity of this?"
Yousufzai drew the ire of the Taliban for defending her right to an education. The outspoken teen had carried out her campaign since the age of 11 through an online diary she wrote for the BBC.
"Support education! Support the people who support women!" Madonna went on to shout to the appreciative crowd Wednesday.
To emphasize her point later in the show, the 'Vogue' hitmaker rolled down her trousers to reveal the word "Malala" scrawled across the small of her back, said The Hollywood Reporter.
"This song is for Malala," she said, before launching into a performance of her hit song, "Human Nature."
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Hollywood stars like Jessica Alba, Heidi Klum and Neil Patrick Harris were in attendance at the show.
Yousufzai is not the only subject Madonna has drawn attention to during her tour. While onstage in Moscow she made an impassioned plea for the release of jailed Russian punk band Pussy Riot.