Fully siliceous layer-by-layer assembled thin films, using polyhedral oligomeric silsesquioxanes (POSS) as building blocks, were successfully deposited on various substrates, including cotton fabric. Water-soluble OctaAmmonium POSS ((+)POSS) and OctaTMA POSS ((-)POSS) were used as cationic and anionic components for thin film deposition from water. Aminopropyl silsesquioxane oligomer (AP) was also used as an alternative cationic species. The thickness of the AP/(-)POSS and (+)POSS/(-)POSS film is shown to increase linearly with bilayers deposited. Thermogravimetric analysis (TGA), vertical flame testing (VFT), microscale combustioncalorimetry (MCC) and pill testing were performed on cotton fabric coated with 5–20 bilayers of a given recipe. All coated fabrics showed improved preservation (i.e., greater residue following heating to 600 °C) and resistance to degradation from direct flame. With less than 8 wt % added to the total fabric weight, more than 12 wt % char remained following MCC for the 20 bilayers (+)POSS/(-)POSS coated cotton. Furthermore, afterglow time was reduced and the fabric weave structure and shape of the individual fibers were highly preserved following VFT. It is expected that this environmentally-friendly coating could be used to impart flame retardant behavior to a variety of fabrics, for protective clothing and soft furnishings, and other complex substrates like foam.