Background <p>Psoriasis, a prevalent autoimmune skin condition, considerably impairs the quality of life of those who are affected by it. Several studies have demonstrated that obesity significantly contributes to both the onset and progression of psoriasis. Relative fat mass (RFM), a novel obesity index, provides a more precise measure by incorporating both height and waist circumference (WC). The aim of this study was to investigate the association between RFM and psoriasis risk, taking into account the intermediary role played by the systemic inflammation response index (SIRI).</p> Methods <p>The cross-sectional study assessed data from 8,479 adults who participated in the NHANES cycles from 2003 to 2006 and 2009 to 2014. To examine the association between RFM and psoriasis, both multivariate logistic regression model and restricted cubic spline (RCS) analyses were conducted. A mediation analysis was used to clarify the role of SIRI in the association between RFM and psoriasis.</p> Results <p>Higher RFM was significantly associated with a 5% higher risk of developing psoriasis (odds ratio [OR] = 1.05, 95% confidence interval [CI]:1.02–1.08), with RFM quartiles indicating a significant trend (<i>P</i> _{for trend} &lt; 0.05). The SIRI demonstrated a significant mediating effect on the RFM-psoriasis relationship (mediation effect ratio = 5.02%).</p> Conclusion <p>Elevated RFM are associated with an increased prevalence of psoriasis. RFM has the potential to be a beneficial anthropometric measure for more accurately predicting psoriasis risk.</p>