Parrish signed with the San Francisco 49ers on a five-year deal following the 2001 NFL Season. Prior to the 49ers April minicamp, Parrish has his right testicle removed in an operation after discovering a tumor in an exam on a nagging groin injury. In his first season with the 49ers, Parrish recorded seven interceptions. Parrish’s most notable game in 2002 with the 49ers was in week 14 against the Dallas Cowboys, when Parrish recorded two interceptions with a bulky arm brace because he was playing with a recently dislocated elbow. Parrish received NFC Defensive Player of the Week for his game against Dallas that helped secure a victory. The San Francisco 49ers went on to win the NFC West in Parrish's first year with a 10-6 overall record.