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Objective To ascertain plasma levels of heat shock protein 90α (HSP90α) and squamous cell carcinoma antigen (SCC-Ag) and their diagnostic potential in cervical cancer. Methods In a cross-sectional study, patients’ cervical tissue samples were screened for high risk (HR) human papilloma virus (HPV) DNA and underwent a thinprep-liquid based cytology test (TCT). Plasma samples were analysed by enzyme-linked immunosorbent assay (ELISA) for HSP90 α and SCC-Ag levels. Results Of the 295 women who underwent screening, 75 were healthy controls 75 (HR-HPV −ve TCT −ve ), 110 were HR-HPV +ve , TCT −ve and 110 were HR-HPV +ve TCT +ve . There were significant differences between levels of HSP90α and SCC-Ag proteins across the patient groups with those positive for cervical cancer having the greatest levels of proteins compared with other groups. For patients with high grade SCC there was a significant correlation between levels of HSP90α and SCC-Ag. The area under the ROC curve for combined HSP90α*SCC-Ag was the largest compared with the single proteins. Using a cut-off value of 16.4 ng/ml to delineate cervical cancer diagnosis, the sensitivity and specificity of HSP90α*SCC-Ag were 90.3% and 95.1% respectively. Conclusion Plasma HSP90α protein levels correlated well with SCC-Ag levels in patients with cervical cancer and the combination of HSP90α*SCC-Ag may be a useful diagnostic biomarker.