Objective:To investigate the expression and clinical significance of long non-coding RNA (lncRNA) H19 and lncRNA maternally expressed gene 3 (MEG3) in the serum of patients with gastric cancer (GC).Methods:A total of 87 GC patients admitted to the First People′s Hospital of Suqian (July 2017 to August 2018) were selected as the GC group, 51 patients with benign tumors as the benign tumor group, and 40 healthy people with physical examination as the healthy control group. The expression levels of lncRNA H19 and lncRNA MEG3 in serum were measured; the relationship between the expression levels of the two and clinicopathological features and prognosis of patients with GC was analyzed.Results:The levels of serum lncRNA H19 in healthy control group, benign tumor group and GC group were gradually increased, and lncRNA MEG3 level was gradually decreased ( P<0.05); the serum lncRNA H19 level in GC group was related to tumor invasion depth, tumor node metastasis (TNM) stage and lymph node metastasis. The level of lncRNA MEG3 was related to the degree of differentiation, TNM stage and lymph node metastasis ( P<0.05). Among the 87 GC patients , 63 patients were followed up for 13-32 months with an average of (23.54±4.18)months. Kaplan Meier survival curve showed that the overall survival rate of high serum lncRNA H19 group and low serum lncRNA MEG3 level group was significantly lower than that of low serum lncRNA H19 level group and high serum lncRNA H19 level group. Multivariate Cox regression analysis showed that lncRNA H19 ( HR=3.442, 95% CI=0.089-23.421) was an independent prognostic factor for GC patients, and lncRNA MEG3 ( HR=4.386, 95% CI=0.934-20.596) was a protective factor ( P<0.05); receiver operating characteristic (ROC) curve showed that the sensitivity, specificity and accuracy of serum lncRNA H19+ lncRNA MEG3 [area under curve (AUC)=0.922, 95% CI=0.861-0.962] were higher than those of serum lncRNA H19 (AUC=0.840, 95% CI=0.771-0.904) and lncRNA MEG3 (AUC=0.830, 95% CI=0.753-0.890). Conclusions:The level of serum lncRNA H19 in GC patients is significantly increased, and the level of lncRNA MEG3 is significantly reduced, which is closely related to tumor occurrence, development and prognosis. Combined detection of the two can enhance the diagnostic value of GC.