In clinical practice, we found that some primary gastrointestinal mucosa-associated lymphoid tissue (MALT) lymphoma had different prognosis. This study aimed to explore the role of IGH rearrangement, p53 and ATM gene variations in the assessment of prognosis in primary gastrointestinal MALT lymphoma. In 50 cases of primary gastrointestinal MALT lymphoma (1) IGH arrangement was found in 59.5% of patients with primary gastrointestinal MALT lymphoma; IGH arrangement was found in 48.4% of patients with primary gastrointestinal MALT lymphoma at stage I-II and in 90.9% of patients at stage III-IV (χ(2) = 6.093, p < 0.05). Average survival time in patients with IGH rearrangement was 16.39 months, being shorter than that in patients with non-IGH rearrangement (38.13 months) (t = 3.239, p < 0.01). (2) p53 gene deletion was found in 31.0% of patients with primary gastrointestinal MALT lymphoma; p53 gene deletion was found in 22.6 % of patients with primary gastrointestinal MALT lymphoma at stage I-II and in 54.5% of patients at stage III-IV (χ(2) = 3.882, p < 0.05). Average survival time in patients with p53 gene deletion was 8.0 months, being shorter than that of patients with normal p53 gene (32.81 months) (t = 3.609, p < 0.01). (3) ATM gene deletion was found in 23.8% of patients with primary gastrointestinal MALT lymphoma; ATM gene deletion was found in 16.1 % of patients with primary gastrointestinal MALT lymphoma at stage I-II and in 45.5% of patients at stage III-IV (χ(2) = 3.849, p < 0.05). Average survival time in patients with ATM gene deletion was 6.10 months, which is shorter than that of patients with normal ATM gene (31.71 months) (t = 3.503, p < 0.01). (4) IGH rearrangement, p53 and ATM gene deletion were no correlation with tumor location. (5) Average survival time in primary gastrointestinal MALT lymphoma patients of non-gene or single gene change was 33.42 months, which is longer than that of patients with multiple genes change (6.67 months) (t = 4.013,p < 0.01). There was a high incidence of IGH rearrangement or p53 and ATM gene deletion in patients at stage III-IV. The average survival time was shorter in these patients. Average survival time in primary gastrointestinal MALT lymphoma patients with multiple genes abnormalities was shorter than that in non-gene or single gene change patients. IGH rearrangement, p53 and ATM gene deletion may play a synergistic role in the occurrence and development of the primary gastrointestinal MALT lymphoma. Patients with multiple genes abnormalities had poor prognosis, and they should be advised early united chemotherapy.