Peritoneal dissemination is one of the most common causes of metastasis from malignancies in the abdominal cavity. However, the treatment of peritoneal dissemination is difficult; patients receiving normal chemotherapy have a 0-1% chance of surviving for 5 years. Milky spots in the greater omentum are considered to facilitate the adhesion and invasion of abdominal free cancer cells, and subsequently lymph node metastasis occurs. Since immune cells such as macrophages and lymphocytes are present in the greater omentum and lymph nodes, the activation of immune cells would be a promising strategy for treatment. Single-stranded oligonucleotides containing CpG dinucleotides (CpG DNA) are recognized by Toll-like receptor-9 on antigen-presenting cells such as macrophages to stimulate Th-1-type immune responses. However, a delivery system for CpG DNA to immune cells is essential to develop effective therapy against peritoneal dissemination. Here we review the pathophysiologic basis of peritoneal dissemination and introduce our approach that employs cationic liposomes as a carrier for CpG DNA as a new approach in the treatment of peritoneal dissemination.