To evaluate the stiffness of tongue squamous cell carcinoma (TSCC) using ultrasound strain elastography, a relatively new sonographic imaging technique, and to identify the factors that affect this stiffness. We treated 62 patients diagnosed with muscle invasive TSCC, who were treated at the department of oral surgery of our institution. Each patient’s tumor stiffness was semi-quantified according to the ratio of cancer to tongue muscle strain measured using ultrasound strain elastography (the strain ratio). Histopathological diagnosis was made on the same section as the ultrasound strain elastography. We set the following histopathological parameters: cancer cell content in the tumor area (%CCC), collagen fiber content in the tumor area (%CFC), and tumor-infiltrating inflammatory cell content in the stromal compartment (%TIIC). Spearman's rank correlation (rs) was used to assess correlations, and P values