Liquid repellent surfaces are being promisingly applied in industry and our daily lives. Herein we report a facile and effective sol–gel method for fabricating hybrid coatings with highly omniphobic and self-cleaning properties. The fluorinated hybrid nanocomposite was synthesized via one-step hydrolytic condensation of a nanosilica sol, methyltriethoxysilane (MTES) and 3-[(perfluorohexyl sulfonyl) amino] propyltriethoxysilane (HFTES). The solvent mixture of water and 2-propanol surrounding the hydrophobic nanosilica is a key factor in the control of nanoparticle aggregation, which leads to the formation of a multi-scale roughness surface with different wettabilities. The fluorinated nano-sol can be easily coated on various hard and soft substrates by spraying or dipping methods, endowing the substrate with omniphobicity to different organic liquids and biofoulings especially solidified egg white. Furthermore, the designed coating shows excellent self-cleaning and anti-adhesion properties in various harsh environments such as high temperature, acid and alkaline treatment and oil contamination. Owing to the facile method and its remarkable omniphobic abilities, the fluorinated hybrid coatings can be expected to have potential industry applications in a material system requiring robust antifouling, protein resistance and self-cleaning functions.