Hydrophobicity property of polystyrene (PS) thin film is one of the essential factors to be considered in the development of quartz crystal microbalance (QCM) biosensor using polystyrene as matrix layer. Many methods were developed to improve the immobilization rate of the biomolecule on the sensor surface without affecting the QCM essential works. Surface modification of the sensor surface aims to modify the physical and or chemical property of the surface. A straightforward method, the fast, environmentally-friendly, and low-cost solution to modify the sensor surface coated with polystyrene film is using oxygen plasma. In this experiment, the polystyrene film was spin-coated on both surface of QCM electrodes and then heated at 100 °C. The specimen is then placed for 5 min long in a chamber filled with oxygen plasma generated by 2 MHz RF-DC high-density plasma system. The relationship between DC-bias used and the changes in morphology properties of the coated film was characterized by Topography Measurement System (TMS) and Contact Angle Measurement. The electrical characteristic of QCM was also characterized using Impedance Analyzer. It was revealed that the contact angle of oxygen plasma treated film is changed and depicted the hydrophobic character. Also, there is an increasing resonance frequency of the sensor after oxygen plasma treatment indicates an etching mechanism occurs during plasma treatment.