Freddie hammered his half-ton off 79 balls with nine fours and one six.
Having resumed the day on 36, the England all-rounder eventually reached 54 before being caught by Michael Lumb in the slips attempting to pull Dimitri Mascarenhas.
Flintoff's 86-ball innings was his first half-century for Lancashire since the Twenty20 Cup quarter-final defeat against Middlesex last July.
Flintoff, who is hoping to feature in the Ashes series, later bowled three overs for 12 runs. Hampshire take 20 points from the match.
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