Objective To analyze the relationship between peripheral blood microRNA-18a-5p (miR-18a-5p), fibrinogen (FIB)-to-lymphocyte ratio (FLR) and neutrophil-to-lymphocyte ratio (NLR) and prognosis in patients with advanced gastric cancer.Methods The 102 patients with advanced gastric cancer admitted to Nanjing Jiangning Hospital from December 2019 to March 2024 were selected. The neutrophil and lymphocyte counts were detected by automatic blood cell analyzer before treatment to calculate the NLR, while FIB was determined by immunoturbidimetry for FLR calculation. The expression of miR-18a-5p was detected by quantitative real-time polymerase chain reaction. Patients received chemotherapy and were followed up through outpatient visits and telephone consultations until October 31, 2024. Based on their prognosis, they were classified into a good prognosis group and a poor prognosis group (patients who experienced distant metastasis, recurrence, or death). The clinical data of patients in the good prognosis group and the poor prognosis group were compared to analyze the factors affecting the poor prognosis of patients with advanced gastric cancer, and the receiver operating characteristic (ROC) curve was plotted to determine their predictive values.Results Of 102 patients with advanced gastric cancer, 24 had poor prognosis, and the rate of poor prognosis was 23.59%. The poor prognosis group had a higher proportion of poorly differentiated tumors, a higher percentage of stage IV cases, as well as elevated FLR, NLR, and relative expression levels of miR-18a-5p compared to the good prognosis group (P <0.05). Stepwise multivariable Logistic regression analysis revealed that poorly differentiated tumors [O^R = 4.240 (95% CI: 1.603, 11.217) ], stage IV tumors [O^R = 4.833 (95% CI: 1.832, 12.752) ], and higher FLR [O^R = 4.750 (95% CI: 2.072, 10.889) ], NLR [O^R = 3.481 (95% CI: 1.767, 6.858) ], and relative expression of miR-18a-5p [O^R = 2.548 (95% CI: 1.566, 4.146) ] were risk factors for poor prognosis in patients with advanced gastric cancer (P < 0.05). ROC curve analysis showed that the sensitivities of FLR, NLR, miR-18a-5p levels and together for predicting poor prognosis in patients with advanced gastric cancer were 79.20% (95% CI: 0.673, 0.910), 62.50% (95%CI: 0.506, 0.744), 75.00% (95% CI: 0.631, 0.869) and 87.5% (95% CI: 0.756, 0.994), with the specificities being 70.50% (95% CI: 0.586, 0.824), 73.10% (95% CI: 0.612, 0.851), 67.90% (95% CI: 0.561, 0.798), and 85.9% (95% CI: 0.740, 0.978).Conclusion The combination of FLR, NLR and miR-18a-5p has a high value in predicting the poor prognosis of patients with advanced gastric cancer.