Introduction Gastric cancer remains one of the leading causes of cancer mortality worldwide, characterized by an aggressive pathogenesis associated with oncogene mutations (MYC, KRAS) and inactivation of tumor suppressors (p53, PTEN). MicroRNAs (miRNAs), as key epigenetic regulators, play a dual role in carcinogenesis: oncomirs (for example, miR-21, miR-223) enhance oncogene expression, suppress apoptosis and promote proliferation, migration, and invasion of cells via the PI3K/AKT and MAPK pathways; conversely, tumor-suppressive miRNAs (miR-34, miR-101) inhibit MYC and KRAS, stabilize p53 and PTEN, thereby slowing metastasis and angiogenesis. In the structure of cancer incidence and mortality in the Russian population, gastric cancer ranks second among men and third among women. Approximately 1.0–1.1 million new cases of gastric cancer are diagnosed worldwide each year, and up to 50,000 new cases are detected in Russia. About 760,000–800,000 people die from the disease worldwide annually. Objective Analysis of the role of microRNAs in regulation of the tumor-suppressor balance. Materials and methods Clinical biopsy specimens of gastric mucosa from 120 patients with adenocarcinoma and paired samples of histologically normal tissue were used, as well as the cell lines AGS, MKN45, and GES-1. miRNA and target protein expression were assessed by molecular-biology methods, and statistical analysis was performed taking into account correlations, survival, and significance levels. Results The study demonstrated a pronounced microRNA imbalance in gastric adenocarcinoma: oncogenic miR-21 and the miR-17-92 cluster are upregulated, while tumor-suppressive miR-34a and miR-200 are downregulated. This reflects a shift toward proliferation, invasion, apoptosis suppression, and increased tumor aggressiveness. Discussion In this section the results are compared with literature data and their biological and clinical implications are discussed. It is emphasized that the disrupted microRNA balance shapes an aggressive tumor phenotype, and that miRNAs themselves can be considered potential markers of progression. It is noted that the imbalance between oncogenic and tumor-suppressive miRNAs determines invasiveness, metastasis, and clinical prognosis. Conclusion The study investigated the involvement of microRNAs in the development of gastric adenocarcinoma. The obtained results confirm the significance of microRNAs as potential therapeutic targets in gastric cancer.