Tyrosine phosphorylation plays an important role in regulating human physiological and pathologicalprocesses. Functional stabilization of tyrosine phosphorylation largely contributes to the balanced, coordinatedregulation of protein tyrosine kinases (PTKs) and protein tyrosine phosphatases (PTPs). Research has revealedPTPs play an important suppressive role in carcinogenesis and progression by reversing oncoprotein functions.Receptor-type protein tyrosine phosphatase O (PTPRO) as one member of the PTPs family has also been identifiedto have some roles in tumor development. Some reports have shown PTPRO over-expression in tumors can notonly inhibit the frequency of tumor cell division and induce tumor cell death, but also suppress migration. However,the tumor-suppression mechanisms are very complex and understanding is incomplete, which in some degreeblocks the further development of PTPRO. Hence, in order to resolve this problem, we here have summarizedresearch findings to draw meaningful conclusions. We found tumor-suppression mechanisms of PTPRO to bediverse, such as controlling G0/G1 of the tumor cell proliferation cycle, inhibiting substrate phosphorylation,down-regulating transcription activators and other activities. In clinical anticancer efforts, expression level ofPTPRO in tumors can not only serve as a biomarker to monitor the prognosis of patients, but act as an epigeneticbiomarker for noninvasive diagnosis. In addition, the re-activation of PTPRO in tumor tissues, not only caninduce tumor volume reduction, but also enhance the susceptibility to chemotherapy drugs. So, we can proposethat these research findings of PTPRO will not only support new study ideas and directions for other tumorsuppressors,importantly, but also supply a theoretical basis for researching new molecular targeting agents inthe future.