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Background: Gastrointestinal stromal tumors (GIST) includes a group of mesenchimal tumors. One of the studied issues is the relation between the survival of the patient and protein S-100. We intended to study these types of tumors to understand whether there is any relationship between protein S-100 and survival rate. Methods: In this survival study, 40 patients who with stromal cancer of gastrointestinal tract admitted in AL-Zahra hospital, Isfahan were assessed. These patients were found by studying all the pathological reports recorded in hospital archives. Finding: Forty patients (62.5% male vs 37.5% female) with the mean age of 58.4 ± 16.6 enrolled in study. 12.5% of patients were younger than 40 years old. Protein S-100 was positive just in 17.5% of these patients. 80% of patients have been alive since the end of the study and 20% were dead. The average time of survival from the beginning of diagnosis was 63 ± 4.4 months. Conclusion: Although there are different results about the effect of this protein on prognosis and survival of patients, but protein S-100 is yet considered to be an effective factor on survival and prognosis of these types of tumors and more studies should be carried out to in this field.