Filamin A, an actin cross-linking protein, consists of two subunits that dimerize through C-terminal self-association domain. Each subunit contains an N-terminal spectrin-related actin-binding domain followed by 24 immunoglobulin-like (Ig) repeats. Two flexible hinges separate the 24 Ig repeats into rod 1 (repeats 1-15), rod 2 (repeats 16-23), and self-association domain 24. Filamin A not only supports the tension of actin network but also interacts with many transmembrane and signaling proteins mostly in the rod 2 segment. By using high force magnetic tweezers, the force response of Filamin A was studied. We found that rod 2 segment is susceptible to ~10 pN force, while the rod 1 segment can withstand significantly higher forces. Physiological-relevant-force-induced conformation change in rod 2 segment is from the disruption of domain pair interaction, which supports the mechano-sensing function of Filamin A.