A commercial Niobium–Hafnium–Titanium (Nb-Hf-Ti) alloy (C-103), produced by vacuum arc remelting (VAR), showed clear signatures of internal oxidation viz. presence of monoclinic-HfO2 at all the grain boundaries. Minor cold rolling, to ∼10% reduction in thickness, initiated cold cracking. This was observed at some, but not all, of the high angle Nb–Nb grain boundaries containing coarse HfO2 2nd phase oxide precipitates. Closer microscopic examination revealed cold cracking at selective Nb-HfO2 interfaces. There appeared no clear mesoscopic experimental rationale behind this selective interfacial cold cracking. In order to understand this, density functional theory (DFT) calculations were performed on the metal-oxide interface models. They showed significant separation or decohesion energy difference (∼76%) with different atomistic bonding at the terminating layer of the Nb-HfO2 interface. In particular, the interface with one atomic layer of Nb bonded with oxygen of HfO2 had very low work of separation, which was about ∼8% lower than the Nb–Nb interface of the bulk Nb. In brief, the DFT simulations brought out the defining role of metal-oxide interface’s terminating layer on the interface decohesion. This is in agreement with the past theoretical research performed on several metal||non-metal interfaces. The present study extends this hypothesis to a practical example of selective cold cracking of a commercial Nb-Hf-Ti alloy. •Nb-Hf-Ti alloy (C-103) showed signature of internal oxidation: formation of HfO2 at all the grain boundaries.•On ∼10% deformation, the alloy experienced cold cracking at selective grain boundaries (GBs) containing coarse 2nd phase HfO2.•Extensive microtexture measurements could not identify the rationale behind the selective grain or phase boundary cold cracking.•Density functional theory calculations showed that the … NbNb||NbOHfO … interface has the lowest work of separation for the cold cracking to be initiated.