Infectious agents are implicated in the development of various cancers, with Helicobacter pylori (H. pylori) frequently detected in gastric cancer patients. This study aimed to evaluate the expression of the SMOX gene in a cohort of Polish gastric cancer patients. SMOX is proposed to facilitate H. pylori-mediated carcinogenesis through mechanisms involving inflammation, DNA damage, and activation of β-catenin signaling. Additionally, we analyzed mRNA expression of selected pro-inflammatory cytokines (IL-2, IFN-γ, TNF-α) and the antimicrobial peptide cathelicidin (CAMP). Gastric tissue samples were obtained during total gastrectomy from three locations: the primary tumor, tissue 3 cm away from the tumor, and tissue from the opposite gastric wall. RNA was extracted, and quantitative PCR (qPCR) was performed to assess gene expression levels. SMOX expression was significantly elevated in gastric cancer tissues from patients with a history of H. pylori infection. To our knowledge, this represents the first study evaluating SMOX expression in patient-derived gastric tissue rather than in cell lines. Expression of pro-inflammatory cytokines (IL-2, IFN-γ, TNF-α) was also increased, suggesting their involvement in shaping the tumor-associated inflammatory microenvironment. In contrast, CAMP expression was reduced across all examined tissue types. The data support a role for SMOX in gastric carcinogenesis, potentially linked to H. pylori infection and inflammatory signaling. Further studies are warranted to clarify the contribution of inflammatory mediators and other factors, which may inform future cancer immunotherapy strategies.