Mycosis fungoides (MF) is the most common T-cell lymphoma in cutaneous malignant lymphoma, which may involve multiple organs in the advanced stage with a poor prognosis. Till now, early identification of the disease is still urgent and also there is no optimal therapy for advanced MF. In the present study, quantitative proteomic analyses (Label Free Quantitation, LFQ) and a parallel reaction monitoring (PRM) assay were applied in tissue samples of different stages of MF and the control group, so as to conduct preliminary molecular analysis of the significantly expressed proteins which may involve in the pathogenesis of the disease. The results revealed that genes and proteins implicated in DNA replication initiation, nucleosome assembly, cell adhesion activity, together with the cellular component and molecules that connecting extracellular region part may be involved in the pathogenesis and metastasis of MF. Some special proteins expressed obviously differently from the early to advanced stage of MF, indicating that they may be the key molecules for the progression of the disease. We believe that proteomics is a powerful tool to identify potential biomarkers for diagnosis and these molecules may be promising therapeutic targets for MF. For that, further studies are still needed.