Oil-in-water emulsions consisting of squalene, tween and/or span have shown significant benefits for the prevention and control of influenza, with their adjuvant efficacy enhancing the immunogenicities of influenza vaccines in high-risk groups. However, concerns have been raised following reports that post-immunization reactions associated with these adjuvanted vaccines are more frequent. In this work, a stable and biocompatible oil-in-water emulsion adjuvant containing squalene, egg lecithin and sodium oleate has been developed. Animal studies demonstrated that this adjuvant could induce strong immune responses in BALB/c mice, as measured by hemagglutinin inhibition titers, influenza-specific serum antibody titers and cytokine levels (IFN-γ and IL-4). Different oil compositions, including squalene, medium chain triglyceride and long chain triglyceride, were also evaluated. Furthermore, in contrast to MF59(®) which can only be sterilized by aseptic filtration, this adjuvant remained stable during autoclaving, showing minimal changes in pH, particle size and lysolecithin concentration.