Abstract The objective of this study was to evaluate cytokines in unstimulated whole saliva (UWS) of oral squamous cell carcinoma (OSCC) patients as compared to those with pre- and post-operation for evaluation as markers of OSCC. Sixteen OSCC patients were included in this study. Cytokine concentrations in resting saliva were measured using a Bio-Plex suspension array system. Only interleukin-1 (IL-1) beta showed significantly different cytokine concentration in saliva between pre- and post-operation. IL-1 beta was released from cultured OSCC cells confirmed by ELISA and immunohistochemistry. From this study, IL-1 beta in UWS may be useful for detection of early stage OSCC. More studies are needed to accept the utility of IL-1 beta in UWS for predicting, diagnosis and evaluation of OSCC.