Biological functions in a cell are mostly governed by biomolecules. Protein functions are also tightly regulated by their three-dimensional structures via communicating genetic information. Human disease-related proteins in signal process have been extensively reported in the point of protein structures. Structural biophysics together with biochemical techniques such as NMR spectroscopy, fluorescence and X-ray crystallography has been served as a major method in understanding structure and function of proteins in atomic scale. Very recently, it has been demonstrated that non-thermal plasma irradiation can be applied to living cells and tissues for clinical purpose. A new cancer therapy by non-thermal plasma irradiation has been proposed for DNA damage and mitochondria dysfunction in mammalian cells. In this presentation, I demonstrate that non-thermal plasma irradiation could affect cellular signaling and molecular event medicated by proteins in a cell by modern biophysical techniques. I will also discuss plasma effect on protein folding which are important in understanding functional modification mediated by proteins of the living cells in the presence of plasma irradiation.