Update publication information. Glioblastoma multiforme (GBM) is the most lethal brain malignant neoplasm, associated with poor prognosis and high recurrence. The mechanisms involved in GBM development and recurrent remains largely unknown. Hence, it’s considerably imperative to explore the potential targets and unravel the mechanism implicated in GBM tumorigenesis and recurrence. In our study, mass spectrometry-based label-free quantitative proteomics was employed to explore the proteomic profiling in non-paired samples of primary and recurrent GBM. Bioinformatic analysis of differentially expression proteins (DEPs) were applied to screen the hub genes. Subsequently, hub genes expression was verified by western blot and immunohistochemistry (IHC) in GBM tissues, followed by its biological effect on GBM at a cellular level determined. We contoured the divergent landscape of proteome between primary and recurrent GBM, with only ten overlapped DEPs included. The several hub genes screened (e.g., CKAP4 and CANX) and enriched pathways correlated with primary GBM such as post-translation, metabolism, energy pathways and cell growth were profiled. Furthermore, CKAP4 was implicated in proliferation, migration and invasion of A172 and T98G cell lines. However, UQCRC1, together with relative enriched pathways such as oxidative phosphorylation, were screened in recurrent GBM. Establishment of the proteomics and several candidate proteins identified could pose considerable access to understand complex biochemical processes and obtain a better picture of GBM biology.