microRNAs have been shown to be stable and detectable in circulating blood, and circulating microRNAs are specifically expressed in numerous diseases. However, to date, the association between microRNAs and osteonecrosis of the femoral head (ONFH) has remained elusive. It was hypothesized that specific microRNAs in the serum of ONFH patients may participate in the pathogenesis of ONFH. In the present study, therefore, the ONFH‑specific serum microRNAs were screened using deep sequencing technology. Peripheral blood serum was collected from three steroid‑induced ONFH patients with systemic lupus erythematosus (SLE), three SLE controls and three healthy controls, respectively. Total RNA was extracted from the serum and a microRNA cDNA library was built. High‑throughput sequencing was then used to sequence the serum microRNAs of the samples and screen differentially expressed serum microRNAs in patients with steroid‑induced ONFH. 27 differentially expressed microRNAs from ONFH serum were selected; of these, 15 microRNAs were over‑expressed and 12 were under‑expressed compared with SLE controls and healthy controls. The present study showed that abnormally expressed microRNAs existed in the serum of ONFH patients and therefore have the potential to be diagnostic markers.