Background <p>Differences in symptom presentation of schizophrenia in male and female patients may be related to differences in physiological and hormonal levels between genders. The aim of this study was to investigate the potential association of thyroid hormones with positive and negative symptoms in schizophrenic patients of different sex.</p> Methods <p>In this study, a total of 158 male and 160 female schizophrenia patients were retrospectively selected from our hospital between January 2023 and July 2025. Their clinical data were analyzed retrospectively. Venous blood samples were collected to measure levels of T3, T4, FT3, FT4, and TSH. The relationship between thyroid hormone levels and the positive symptom scores (SAPS), including its subscales (delusional ideas, hallucinations, bizarre behavior, and formal thought disorders), as well as the negative symptom scores (SANS), encompassing its subscales (expression and motivation and pleasure ), was subsequently analyzed.</p> Results <p>Male and female patients with schizophrenia showed significant differences in the severity of both positive and negative symptoms. There was a significant interaction between sex and TSH with negative symptoms (<i>p</i> &lt; 0.001). In sex-stratified regression analyses, TSH was positively associated with negative symptoms in male patients (<i>p</i> &lt; 0.001), while both T3 and T4 exhibited negative associations with negative symptoms in both male and female patients (all <i>p</i> &lt; 0.05).</p> Conclusions <p>Our research indicates that thyroid hormone levels are associated with the severity of schizophrenia symptoms and vary by sex, highlighting the importance of considering sex differences in clinical practice.</p>