Candida albicans (CA) is a frequent opportunistic pathogen in cancer patients. Usually, human surfaces are protected, apart from physical barriers, by the production of human beta-defensins (hBD). hBD-2 shows a potent antimicrobial activity against CA. We therefore investigated whether CA induces hBD-2 expression in primary oral cells and if immunosuppressive betamethasone alters hBD-2 expression. Additionally, we studied, whether a lack of hBD-2 expression could explain opportunistic infection of tonsillar cancer. Primary oral epithelial cells and fibroblasts were stimulated with Candida albicans in a time- and dose-dependent manner with or without betamethasone preincubation. Total RNA from oral cells and specimens was isolated and hBD-2 expression was analyzed by semiquantitative RT-PCR. Our data demonstrate that opportunistic CA induced hBD-2 expression in a time- and dose-dependent manner, suggesting hBD-2 to be a fast antifungal, epithelia-derived immune response. Treatment with glucocorticoid could lead to diminished innate immunity based on suppression of inducible AP. Malignant transformation induces alteration of hBD-2 expression and leads to a reduced hBD-2 expression and subsequentially to Candida colonization on oral SCCs.