Anophthalmic patients not only cause obvious functional deficits and facial deformities, but lead to poor psychological outcomes, although prosthesis wearing can offer improvements in psychological well-being to some extent. The study aimed to comprehensively evaluate the psychological symptoms and analyze related factors in anophthalmic patients wearing ocular prosthesis. Total of 150 anophthalmic patients and 120 control subjects were included in this cross-sectional study. Baseline characteristics survey and the symptom checklist-90 scale were completed by all participants to assess the psychological symptoms and analyze their related factors by multivariate analysis. The anophthalmic patients exhibited the increased levels of somatization, depression, anxiety, and hostility compared with control subjects. The most prominent symptom was hostility with the median score of 1.20. Female patients presented with higher somatization, depression, anxiety, and hostility. Marital status single was positively associated with depression, anxiety, and hostility symptoms. Lower education and cause of enucleation were related to higher levels of hostility. Anophthalmic patients wearing ocular prosthesis presented with more prominent hostility and somatization besides its higher depression and anxiety symptoms. The findings suggest that for female single anophthalmic patients with low education, especially caused by trauma, timely psychological assessment and intervention should be provided to avoid undesirable consequences.