The present invention provides compositions comprising interfering RNA (e.g.,siRNA, aiRNA, miRNA) that targetpolo-like kinase 1(PLK-1) expression and methods of using such compositions tosilence PLK-1 expression. More particularly,the present invention provides unmodified and chemically modified interferingRNA molecules which silence PLK-1 expressionand methods of use thereof. The present invention also provides serum-stablenucleic acid-lipid particles (e.g., SNALP) comprisingan interfering RNA molecule described herein, a cationic lipid, and a non-cationic lipid, which can further comprise a conjugatedlipid that inhibits aggregation of particles. The present invention furtherprovides methods of silencing PLK-1 gene expression byadministering an interfering RNA molecule described herein to a mammaliansubject. The present invention additionally providesmethods of identifying and/or modifying PLK-1 interfering RNA havingimmunostimulatory properties. Methods for sensitizing acell such as a cancer cell to the effects of a chemotherapy drug comprisingsequentially delivering PLK-1 interfering RNA followedby the chemotherapy drug are also provided.