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Gastrointestinal cancers are considered as the most common type of cancer among men and the second most common cancer in women after breast cancer in Iran. This study was performed to investigate the epidemiology of gastrointestinal cancer in Markazi Province. This is an epidemiological study in which data was gathered from the population-based cancer registry program in the Markazi province of Iran during the years 2010–2014. Data were recorded in Excel software and coded based on ICD-O. All cases out of Markazi provinces were excluded from study, and cases with code C-15-C20 were included in this study. Stata 11 was used to analyze the data. In this study, 2975 new cases of gastrointestinal cancer in Markazi province were included in the analysis. The highest number of cancers was stomach (with 1595 cases), followed by colorectal cancer (980 cases), esophageal cancer (318 cases), and finally small bowl cancer (82 cases). The mean age of gastro-intestinal cancer diagnosis was 65.07 years. The results showed that with increasing age, the incidence of gastro-intestinal cancers increased, and in all sites and both sexes, the highest incidence of gastro-intestinal cancer was in the age group above 70 years. In both sexes, the age specific rate of stomach cancer was higher than other sites (with highest incidence in 2013) followed by colorectal cancer, esophageal cancer, and small bowl cancer. The results showed similar incidence rate of gastrointestinal cancer in Markazi province to other provinces in Iran. This study found that stomach cancer is the most common cancer in the Markazi province; therefore, identifying effective and preventing factors is necessary.