A Photographs of oral cancer cells, SAS-IR (1 × 106 cells/injection, subcutaneous) were injected into the NOD/SCID (NOD.CB17-Prkdcscid/NcrCrl) mice for establishing the tumor xenograft model (n = 5 per group). When tumor size became palpable, mice were separated into four groups: vehicle control, ibrutinib (10 mg/kg, i.p., 5 times a week), cisplatin (5 mg/kg, i.p., once a week), and ibrutinib + cisplatin. B Tumor volume versus time effect curve. Ibrutinib + cisplatin treatment displayed the most significant decrease in tumor volume followed by ibrutinib-only treatment, whereas cisplatin only and vehicle treatments displayed the largest tumor volume. C Kaplan–Meier survival curve. Mice receiving the ibrutinib + cisplatin regimen exhibited the highest survival ratio followed by the ibrutinib only group, whereas the cisplatin only and vehicle groups exhibited the lowest survival ratios. D IHC image of of the xenograft tumors revealed that the ibrutinib/cisplatin combination effectively inhibited the expression of Ki-67 and induction of cleaved capase-3. *p < 0.05; **p < 0.01; ***p < 0.001. Scale bar: 100 μm.