The MYC oncogene/transcription factor is a well-known factor causing tumorigenesis in many tumor types and is deregulated in almost all types of cancers, correlating with advanced aggressive disease and poor survival. The crucial role of MYC-family oncoproteins in cancer development make them attractive targets for therapy in cancer. An interaction between the oncoprotein MYC and VHL has recently been found in the cell nucleus, involving non-proteolytic ubiquitylation of MYC. The possibility that MYC and VHL regulate each other’s function through direct interaction and thereby influence the fate of tumor cells is largely unexplored in the literature and therefore constitutes a new field of research. This project was focused to understand the impact of MYC/VHL interplay on the cell cycle. In order to elucidate the impact of MYC/VHL on the progression of the cell cycle and to detect the expression levels of major cell cycle proteins, flow cytometry and western blot experiments were conducted respectively, on 786-OccRCC and U2OS osteosarcoma MYCER cell lines with regulatable MYC activity and different VHL status. Here, we demonstrate that VHL does not degrade MYC, but rather promotes its expression in 786-O ccRCC as well as VHL stimulated the cells to overcome the checkpoint barriers and progress through the cell cycle. VHL loss or depletion negatively affected MYC’s ability to regulate critical cell cycle proteins and thereby stimulate progression through the cell cycle. The results from this project warrants further investigation on how pVHL affects MYC function.