The influenza A H1N1 pandemic in 2009 highlighted the shortcomings in traditional influenza vaccine production, especially in the time that is needed for a vaccine to become available. Therefore it is important to assess alternative vaccine development strategies. Virus-like particle (VLP) is a potential candidate that may address current problems in vaccine production. In our study, we constructed VLPs which contained the 3 structural proteins, hemagglutinin, neuraminidase and matrix 1 derived from influenza A/Hong Kong/01/2009 (H1N1). VLPs were purified by sucrose density gradient ultracentrifugation and then characterized by Western blotting analysis and transmission electron microscopy. The immune responses and efficacy of protection induced by VLPs were compared with those elicited by the commercial Panenza vaccine in 6-8 week female BALB/c mice. After single dose vaccination with 3 µg of VLPs and equal amount of Panenza vaccine, VLPs could induce higher antibody titer as determined by hemagglutinin inhibition and microneutralization assay. Furthermore, we demonstrated that not only are antibodies to hemagglutinin is higher after VLP vaccination, but VLPs may also induced better antibody response to neuraminidase. In addition, VLP vaccinated mice had better cell-mediated immune response, hence the higher and broader immune responses elicited by VLP vaccination may contribute to its higher efficacy of protection than the commercial Panenza vaccine. As a result, our VLPs conferred 100% protection while the Panenza vaccine only conferred 67% protection. These results indicate that influenza VLPs are highly immunogenic and they are promising to be developed as an alternative strategy to vaccine production in order to control the spread of influenza viruses.