Objective: To investigate the association between ARID1A protein loss and histological differentiation as well as lymph node metastasis in gastric adenocarcinoma, and to further analyze its potential clinicopathological significance.Methods: A retrospective analysis was conducted on 96 patients with gastric adenocarcinoma who underwent radical gastrectomy. All cases had preserved formalin-fixed paraffin-embedded (FFPE) tissue specimens and complete clinicopathological data. Hematoxylin-eosin (HE) staining was performed to evaluate histological differentiation, Lauren classification, lymph node metastasis, lymphovascular invasion (LVI), perineural invasion (PNI), and depth of invasion (pT stage). Immunohistochemistry (IHC) was used to assess ARID1A protein expression, with complete nuclear absence of staining defined as “loss of expression.” Clinicopathological parameters including age, sex, tumor location, Epstein-Barr virus (EBV) status, and microsatellite instability (MSI) status were also collected. The relationships between ARID1A loss and clinicopathological characteristics were analyzed, and multivariate logistic regression was applied to determine independent risk factors for lymph node metastasis.Results: Among the 96 patients, the rate of ARID1A protein loss was 35.4% (34/96). Univariate analysis showed that ARID1A deficiency was correlated with histological differentiation, Lauren classification, lymph node metastasis, pT stage, and EBV status (P < 0.05), but not with sex, age, LVI, PNI, or MSI status (P > 0.05). Multivariate logistic regression analysis demonstrated that pT stage (HR = 2.631, 95% CI: 1.122–6.169, P = 0.026) was an independent risk factor for lymph node metastasis, whereas ARID1A loss did not emerge as an independent factor.Conclusion: Loss of ARID1A expression is correlated with adverse pathological features of gastric adenocarcinoma, including poor differentiation, diffuse Lauren type, and lymph node metastasis, but is not confirmed as an independent risk factor for nodal metastasis. These findings suggest that ARID1A may indirectly contribute to tumor dissemination through its impact on differentiation and invasion depth. ARID1A loss may serve as a potential biomarker for molecular stratification and prognostic evaluation in gastric adenocarcinoma.