Polo-like kinase-1 (PLK-1) belongs to the family of serine/threonine kinases and regulates cell division in the mitotic phase [19,20]. PLK-1 is overexpressed in many types of malignancies and its overexpression is associated with poor prognosis of cancer patients [21,22]. In this review, we discuss possible RNAi strategies against PLK-1 in advanced lung cancers.