Conclusions: The present study indicates that miR-21 is involved in progression from normal to pre-malignant laryngeal lesions (PLLs) and from PLLs to laryngeal squamous cell carcinoma (LSCC). Furthermore, normalized PCR results for miR-21 might be used to discriminate between normal and ordinary hyperplasia before the emergence of dysplasias and pre-malignant lesions with malignant potential. Objective: To investigate a sensitive marker that contributes to progression from normal tissue to PLLs and from PLLs to LSCC. Methods: In 116 PLLs and LSCC patients and 19 without dysplasia matched sets of tissue and plasma samples from Beijing Tongren Hospital, miR-21 was analysed by droplet digital PCR and quantitative real-time polymerase chain reaction based on paraffin-embedded tumour tissue and plasma. Results: Compared with controls, miR-21 levels in tissue and plasma were significantly higher for both PLL and LSCC groups (for both groups vs controls: p <0.0001 for tissue; p<0.05 for plasma). Areas under receiver-operating curves (AUC) for tissue miR-21 were PLL group vs controls: 0.9026 and LSCC group vs controls: 0.8681. For plasma miR-21, AUCs were PLL group vs controls: 0.7355 and LSCC group vs control: 0.6723.