This study aims to examine the expression of androgen receptor (AR) and estrogen receptor (ER) in patients with classic Kaposi's sarcoma (CKS) in Xinjiang, as well as to assess the serum levels of sex hormones in these patients. The objective is to explore potential new directions and targets for diagnosing and treating CKS in Xinjiang. The case group comprised 35 patients diagnosed with CKS who presented at our hospital from 2014 to 2021. The control group consisted of 35 patients with pyogenic granuloma (PG) who visited the hospital during the same period, selected using propensity score matching (PSM). Immunohistochemistry was used to detect AR, human herpesvirus type 8 (HHV-8), and ER in paraffin-embedded tissue samples from patients diagnosed with CKS and PG. Additionally, enzyme-linked immunosorbent assay (ELISA) was used to quantitatively measure serum sex hormone levels in the 35 patients with CKS and 35 patients with PG. AR expression was relatively weak in both the CKS and PG groups, with the PG group exhibiting a slightly stronger expression than the CKS group. Conversely, the expression of ER was significantly higher in the CKS group compared to the PG group (p < 0.05). Additionally, serum testosterone (T) levels were elevated in the CKS group, while serum estradiol (E2) levels were higher in the PG group (p < 0.05). Sex hormones and their receptors are implicated in the pathogenesis of CKS in Xinjiang. The use of ER antagonists may represent a novel avenue for research and treatment of CKS.