P53 is a tumor suppressor and genome guardian factor, and tumor budding is a key link in tumor metastasis. The purpose of this study was to investigate P53 mutation and tumor budding in stage Ⅰ-Ⅱ gastric cancer, to explore the correlation with clinicopathological features, and to reveal the independent prognostic factors of gastric cancer.The data of 588 patients with stage Ⅰ-Ⅱ gastric cancer who underwent radical surgical resection from April 2015 to December 2016 in the Fourth Hospital of Hebei Medical University were retrospectively analyzed and followed up. Immunohistochemistry Envision method was used to conduct P53 staining for paraffin-embedded gastric cancer tissues, and ITBCC recommended tumor budding evaluation method was used to count tumor budding in gastric cancer tissues. The factors affecting the prognosis of gastric cancer were analyzed.There were 209 cases (35.54%) of P53 wild-type and 379 cases (64.46 %) of P53 mutant in 588 patients with stage Ⅰ-Ⅱ gastric cancer. P53 mutation rate were closely correlated with Lauren classification (χ2 =8.152, p = 0.017), degree of differentiation (χ2 =10.495, p = 0.004), number of lymph node metastasis (χ2 =25.550, p < 0.001), and clinical stage (χ2 =7.617, p = 0.016). Tumor budding were closely correlated with Lauren classification (χ2 =194.533, p < 0.001), degree of tissue differentiation (χ2 =22.719, p < 0.001), depth of tumor invasion (χ2 =19.204, p = 0.004), number of lymph node metastasis (χ2 =22.555, p = 0.001), clinical stage (χ2 =10.769, p = 0.005), and vascular tumors bolt (χ2 =12.478, p = 0.002). The higher the tumor budding grade was, the higher the P53 mutation rate was (χ2 =12.933, p = 0.002). Lauren classification (p < 0.001), degree of tissue differentiation (p = 0.005), vascular tumors bolt (p < 0.001) and P53 mutation (p = 0.006) were independent influencing factors for 5-year survival of patients with stage Ⅰ-Ⅱ gastric cancer.P53 mutation status is an independent prognostic factor for gastric cancer patients and a promising cancer treatment target. Tumor budding is a very reliable independent prognostic parameter with important clinical value and should be routinely reported as a biomarker.Copyright © 2022 Elsevier GmbH. All rights reserved.