The 20-year-old will join the Spanish giants at the end of the current season with Bournemouth still having two league matches remaining.
Huijsen joined the Cherries from Italian club Juventus for a fee of £12.6m at the start of the current campaign and impressed in his only season in England.
The English club said in a statement: "AFC Bournemouth can confirm that defender Dean Huijsen will join Real Madrid following the conclusion of the 2024/25 season, with the Spanish side having activated a £50 million release clause.
"Everyone at AFC Bournemouth is looking forward to working with Dean for the remaining two games of the Premier League season, before he embarks on the next step of his career.
"The centre-back, who joined the Cherries from Juventus last summer, has been instrumental in the club's record-breaking campaign, which has seen Andoni Iraola's side already break their highest points tally in the Premier League."
The Spain international has made 34 appearances in all competitions this season, scoring three times with Juventus now getting 10 per cent of Huijsen's fee following the transfer.
Liverpool have reportedly launched an ambitious summer transfer campaign, targeting Bayer Leverkusen's Jeremie Frimpong and Bournemouth's Milos Kerkez to bolster their defensive ranks.
Real Madrid have two matches left in a La Liga campaign that has long lost its competitive edge, with the focus now on finishing strongly and staying injury-free ahead of the Club World Cup in June.
Martin Zubimendi's potential move to Arsenal appeared all but certain, but Real Madrid, led by incoming manager Xabi Alonso, are threatening to derail the Gunners' plans in a bold transfer swoop.
Real Madrid's never-say-die spirit shone through as academy star Jacobo Ramon's stoppage-time winner secured a dramatic 2-1 comeback victory over Mallorca, keeping their faint La Liga title hopes alive.
