Abstract Background Vitiligo, particularly when involving the face, is associated not only with visible disfigurement but also with profound psychosocial consequences. Despite growing interest in the psychosomatic dimensions of skin diseases, the relationship between facial vitiligo and social appearance anxiety remains underexplored. Objective To evaluate the level of social appearance anxiety in patients with facial vitiligo and compare it with healthy controls, and to examine how this anxiety correlates with broader psychological and quality-of-life parameters. In addition, we conducted secondary analyses including subgroup comparisons based on facial lesion localization and moderation analysis using general anxiety as a moderator. Methods A cross-sectional case-control study was conducted among 156 patients with non-segmental facial vitiligo and 143 demographically matched healthy controls. All participants completed the Social Appearance Anxiety Scale (SAAS) and the Hospital Anxiety and Depression Scale. Vitiligo patients additionally completed the Dermatology Life Quality Index and a Visual Analog Scale assessing perceived disease severity. Facial lesion regions were classified anatomically (forehead, periorbital, perioral, mandibular) for subgroup analysis. Moderation analysis was performed to examine whether general anxiety (HADS-A) moderated the relationship between lesion visibility and SAAS scores. Results SAAS scores were markedly higher in the vitiligo group (mean = 55.20 ± 9.17) compared to controls (mean = 19.70 ± 8.40), with a large effect size (Cohen’s d = 4.16; p < 0.001). In patients, SAAS scores were significantly correlated with anxiety (r = 0.753), depression (r = 0.499), quality of life impairment (r = 0.409), and perceived severity (r = 0.605; all p < 0.01). Subgroup analysis revealed significantly higher SAAS scores among patients with periorbital and perioral involvement compared to those with mandibular or isolated forehead lesions (p < 0.05). Moderation analysis confirmed that the strength of association between lesion location and SAAS was significantly amplified in patients with high HADS-A scores (interaction term p < 0.01). Conclusion Facial vitiligo imposes a substantial psychological burden, characterized by elevated social appearance anxiety that extends beyond general psychopathology. Our findings suggest that specific lesion sites, particularly periorbital and perioral areas, are more psychologically distressing and that general anxiety amplifies this impact. These results underscore the need for tailored psychosocial support depending on lesion location and baseline anxiety levels.