Lung cancer is the most frequent cancer for males and third most frequent cancer for females. Targeted therapy drugs based on molecular alterations, such as angiogenesis inhibitors, epidermal growth factor receptor (EGFR) inhibitors, and anaplastic lymphoma kinase (ALK) inhibitors are important part of treatment of NSCLC. However, the quality of the available tumor biopsy and/or cytology material is sometimes not adequate to perform the necessary molecular testing, which has prompted the search for alternatives. This review examines the use of tumor-educated platelet (TEP) as a liquid biopsy in lung cancer patients. The development of sensitive and accurate techniques have made it possible to detect the specific genetic alterations for which targeted therapies are already available. Liquid biopsy offers opportunities to detect resistance mechanisms at an early stage. To conclude, tumor-educated platelet has the potential to be used as liquid biopsy for a variety of clinical and investigational applications.