Background and objectives: Gastric cancer is known as one of the most common cancers and causes of deaths. Early and proper diagnosis is one of the most important things for treatment response. Therefore, this study aimed to determine the expression of p53 , CD44 , Ki-67 , and HER-2/neu markers in the gastric cancer and its relationship with histopathological indicators. Methods: This is a descriptive-analytical study on 60 patientsts with cancer who underwent gastrectomy surgery in 2011-2016 in Shohadaye Tajrish Hospital. The participants were investigated for p53 , CD44, Ki-67 , and HER-2/neu markers’ staining plus demographic characteristics, rate of survival, and histopathological features of the tumors. Results: The mean age of the participants (44 males and 16 females) was 60.25±1.29 years. The patients’ survival rate was 23.82±1.56 months on average. The tumor size was reported as 6.09±2.61 cm and the major tumor type reported was intestinal type (n=40, 66.7%). The level of expression of Ki-67 and CD44 makers was recorded as 33.75 and 24.50%, and p53 and HER-2/neu immunostains were positive in 25 (41.7%) and 20 (33.3%) patients, respectively. The expression of p53 and CD44 markers had no significant relationship with the demographic characteristics, rate of survival, and histopathological features of the tumor of patients (all p>0.05). The expression of p53 gene was associated with a lower rate of survival (p=0.014), while the expression of HER-2/neu was associated with higher probability of developing intestinal type of stomach adenocarcinoma (p=0.010) and ulcerative macroscopic view (p=0.034). Conclusion: This study illustrated that p53 and CD44 markers did not have any diagnostic value in predicting the biological behavior of gastric cancer. In fact, incidence of p53 mmunoreactivity was associated with the lower rate of survival, and the expression of HER-2/neu was associated with higher probability of developing the intestinal type of stomach adenocarcinoma and ulcerative macroscopic view.