Gastrointestinal cancer peritoneal metastasis(GICPM) is one of the biggest challenges of clinical treatment. The ultimate solution to the problem requires the clinicians to accurately understand cytologic and molecular pathological mechanisms behind GICPM, and apply such knowledge in the clinical decision-making process for diagnosis and treatment of individual patient, so as to realize "prevention" and "treatment" proactively. The core cytopathological mechanisms behind GICPM, which are closely related to clinical treatment decisions, are as follows: (1) free cancer cells or clusters in peritoneal cavity colonize the peritoneum, resulting in irreversible pathological damage to peritoneal mesothelial cells; (2) the colonized cancer cells further invade the specific structure of the peritoneal milky spots and initiate an accelerated invasive growth process; (3) the process of peritoneal interstitial fibrosis aggravates the structural destruction of the peritoneum; (4) the interaction between cancer cells and immune cells in the milk spots forms a permissive immune microenvironment that promotes the growth of peritoneal metastatic cancer. These four core cytopathological mechanisms are mutually causal and promote each other, forming a vicious circle of GICPM development. As long as clinicians accurately understand these four points, it is possible to grasp the opportunity of clinical diagnosis and treatment, change reactive and passive treatment into preventive and proactive treatment, and improve the clinical diagnosis and treatment landscape of GICPM.