The catastrophic ductile-to-brittle transition (DBT) at low temperatures fundamentally hinders the engineering implementation of body-centered cubic (BCC) refractory multi-principal element alloys (MPEAs). Here, we reveal that the DBT in a single-phase BCC Ti3Zr1.5NbVAl0.25 alloy is intrinsically governed by the suppression of screw dislocation mobility at lower temperature. Fracture toughness assessments demonstrate a sharp DBT at -38 °C, although the tensile ductility is still larger than 5%. Escalated lattice friction freezes screw dislocations, inducing dislocation multiplication inefficiency that prevents crack-tip shielding and triggering cleavage. This work provides critical insights into the fundamental mechanisms of the DBT in refractory BCC MPEAs.