Purpose: This study investigated the association between Dickkopf-1 (DKK-1) expression and Steroid-Induced Avascular Necrosis of the Femoral Head (SANFH) in patients receiving glucocorticoids (GCs) medication. The role of systemic lupus erythematosus (SLE) disease in this association was also examined. Methodology: This cross-sectional study consists of five matched groups (75 patients): SLE patients or non-SLE patients using GCs and developing SANFH (G1 and G2), SLE or non-SLE patients using GCs and not developing SANFH until three years (G3 and G4), and healthy cases (G5). The necrotic tissues were harvested from thirteen SAFNH patients undergoing core decompression. DKK-1 gene expression was measured using a quantitative real-time polymerase chain reaction (PCR) analysis of peripheral blood and bone tissue. Results: DKK-1 gene expression differed significantly between groups, and GCs groups (G1 to G4) showed significantly greater gene expression than controls (G5) (P<0.05). AVN groups (G1 and G2) expressed the DKK-1 gene 2.5 times more than the control group (G5) (P = 0.034) and 2.0 times more than non-AVN groups (G3 and G4) (P = 0.044). SLE patients with AVN (G1) had 2.1-fold higher DKK1 gene expression than those without AVN (G3) (P<0.05). AVN tissue samples (G1 and G2, n=13) showed 1.8 times higher expression of the DKK-1 gene than controls (P<0.05). Conclusions: Consuming glucocorticoids may increase DKK1 expression, which is a potential mechanism for developing SANFH disease. DKK1 expression might be a prognostic marker for SANFH.