Purpose <p>Autoimmune thyroid disease (AITD) is associated with adverse health outcomes, yet routine thyroid autoantibody testing may not always be practical in general screening settings. The pan-immune-inflammation value (PIV), derived from complete blood counts, represents a simple, low-cost marker of systemic inflammation. This study investigated the association between PIV and thyroid autoantibody positivity in a health examination cohort.</p> Methods <p>This cross-sectional study included 5,785 Chinese adults undergoing routine health examinations at the First Hospital of China Medical University. Associations between PIV and anti-thyroglobulin (TgAb) or anti-thyroid peroxidase (TPOAb) antibody positivity were evaluated using multivariable logistic regression and restricted cubic spline (RCS) models. Subgroup analyses explored interactions with demographic and metabolic factors.</p> Results <p>RCS analyses revealed significant non-linear associations between PIV and TgAb (<i>P</i> for non-linearity = 0.002) as well as TPOAb (<i>P</i> = 0.043) positivity. In fully adjusted models, the highest PIV quartile was associated with an increased risk of TgAb positivity compared to the lowest quartile (OR 1.23, 95% CI 1.03–1.47, <i>P</i> = 0.026). The association with TPOAb was borderline significant (<i>P</i> = 0.061). Notably, the relationship was prominent in females and significantly amplified by hypertension (<i>P</i> for interaction = 0.038).</p> Conclusion <p>Elevated PIV is non-linearly associated with thyroid autoantibody positivity, particularly TgAb, with stronger effects observed in women and hypertensive individuals. As an inexpensive index derived from routine blood tests, PIV may be a useful adjunctive marker for identifying thyroid autoantibody positivity.</p>