Pathogenic processes have been identified that could associate chronic stress and cancer, but these findings have not been observed in oral cancer. This study examined the role of chronic restraint stress on the incidence and severity of OSCC induced with 4-nitroquinoline-1-oxide (4-NQO) in the tongues of CF-1 mice. One hundred twenty CF-1 male mice were divided into 4 groups: (A) received two treatments - restraint stress and induction of chemical carcinogenesis (n = 50); (B) induction of chemical carcinogenesis, without restraint stress (n = 50); (C) restraint stress (n = 10); and (D) control (n = 10). After 30 weeks, tongues were dissected and analyzed by conventional histopathology. The severity of OSSC was analyzed according to the International Histological Classification of Tumors and Bryne's Multifactorial Grading System for the Invasive Tumor Front (ITF). Chronic stress induction was confirmed by plasma corticosterone levels. Results showed that chronic stress was induced with movement restriction (p ≤ 0.05, Mann-Whitney U-test). However, chronic stress did not increase the incidence (p > 0.05, Chi-square) or severity (p > 0.05, Mann-Whitney U-test) of the 4-NQO-induced OSSC in the tongues of CF-1 mice. These results suggest that there is no relationship between chronic stress (induced in mice by restraint) and the incidence and severity of OSSC.