Atmospheric-pressure cold plasma was applied to process the surface of heat-polymerized acrylic resin. Changes to the physical properties and early adherence of Candida albicans were investigated. Alternating current cold plasma with Ar/O2 as working gas was used. Scanning electron microscopy (SEM) and X-ray photoelectron spectroscopy (XPS) were employed to study the possible mechanism. Experimental results showed that after plasma treatment, the contact angle of acrylic resin significantly decreased. There were no significant differences in roughness, flexural strength and elasticity modulus, but microhardness was significant improved in the treated group. More importantly, the early adherence of Candida albicans on the surface was reduced after plasma treatment. Cold plasma seemed to be a promising and convenient strategy of preventing the early adherence of Candida albicans on acrylic resins, which would greatly benefit potential dental applications.