Objective To summarize the new progress of circulating tumor cell markers and their clinical application. Methods The related literatures about the detection and clinical application of circulating tumor cell markers in recent years were reviewed. Resuts Epithelial markers, other markers such as human epidermal growth factor receptor 2 (HER2), estrogen receptor (ER), and immuno-checkpoint genes have also become a useful means to detect the ability of malignant metastasis of circulating tumor cells (CTCs). Moreover, the epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSCs) have also received increasing attention as important CTCs markers owing to their roles in the biological progression of metastasis. Conclusions Through the detection of peripheral blood CTCs, to identify early cancer, monitoring the metastasis and recurrence of cancer and its treatment on all has the very good guiding significance. Signs of circulating tumor cells has great clinical application value in diagnosis and treatment of tumor and prognosis.