Cancer is the second most extended disease during the world with an improved death rate over the past several time. Due to the restrictions of cancer analysis methods, the patient's real survival rate is unknown. Therefore early stage diagnosis of cancer is crucial for its strong detection. Bio-analysis based on biomarkers may help to overcome this problem. Aptamers can be employed as high-affinity tools for cancer detection. The utilization of aptamer-based strategy in cancer investigation and strategy shows new opportunities in biotechnology. The label-free system is an important method to study biomolecules in different sizes, such as biomarkers in real-time because of their greatest sensitivity, selectivity, and multi examination. In this review (with 75 references), excellent features of the label-free aptasensors on the sensitive and accurate monitoring of cancer biomarkers were discussed. Also, the role of advanced of nanomaterials on the construction of label-free aptasensors were investigated. In addition, application of different detection methods such as electrochemical, optical, electronic, and photoelectrochemical (PEC), electrochemiluminescence (ECL) were surveyed. Finally, advantages and limitation of different strategies on the early stage diagnosis of cancer biomarkers were discussed. This article has been updated until July 2020.