Squamous cell carcinoma of esophagus (SCCE) is an aggressive disease with a poor prognosis. Tropomyosins attach to actin microfilaments, providing its stability. Nonmuscle cells express Tpm isoforms such as Tpm1.6 and Tpm1.7 which are involved in cytoskeleton functional properties regulation. The expression of Tpm1.6 and Tpm1.7 was analyzed in SCCE tissues and its association with clinicopathological parameters and survival of patients was assessed. Tpm1.6 and Tpm1.7, besides TPM1 mRNA decreased considerably in SCCE tissues relative to normal esophageal tissues (p < 0.001). TPM1 downregulation level was significantly associated with the degree of tumor differentiation (p = 0.017). Tpm1.6 and Tpm1.7 suppression play a crucial role in esophagus tumorigenesis and could be associated with SCCE poor prognosis.