A novel durable intumescent flame retardant coating, based on metal oxide nanoparticles (NPs) and biomacromolecules, was designed and applied on cotton fabrics. Specifically, different TiO2 NPs/proteins systems were deposited by dip-pad-dry-cure process and the morphology of the resulting coating were assessed by SEM analysis. Enhancement of durability (i.e. resistance to washing treatments) was verified by release tests carried out in static and dynamic conditions. Flammability and cone calorimetry tests were performed for evaluating the fire behavior of the treated fabrics. More specifically, in horizontal flame spread tests, the different nanoparticle/protein based coatings provided an increase of the total burning time and a decrease of the burning rate. Furthermore, the residues at the end of the test were significantly higher with respect to untreated cotton fabric. In particular, casein-based systems seemed to be more effective as compared to the whey proteins counterparts. Cone calorimetry tests showed better fire performances for the coatings based on TiO2/caseins with respect to TiO2/whey proteins, which did not seem to be so effective in protecting the underlying fabric from the heat flux. Therefore, due to their high char-forming character, casein-based coatings may represent an effective and durable fire-resistant finishing alternative to standard flame retardant treatments for cotton.