Objective To study the relationship between cancer-related fatigue (CRF) and clinicopathological features and quality of life in patients with advanced gastric cancer. Methods The clinical and pathological data of 182 patients with advanced gastric cancer were collected, The CRF level and quality of life were assessed by the brief fatigue inventory (BFI), European Organization for Research on Treatment of Cancer (EORTC) life quality scale QLQ-C30 (V3.0). The correlations between CRF and clinicopathological features and quality of life were analyzed. Results One hundred twenty-two patients with advanced gastric cancer were associated with different degrees of fatigue. The CEF BFI score had correlation with the age(F=6.637,P=0.001),PS score(F=15.559,P=0.000),the World Health Organization(WHO) pathologic type (F=7.352, P=0.000). The CRF index of the 50-59 age group was higher than that of other age groups; the CRF BFI scores of PS score 1 and 2 were higher than that of 0 group; CRF BFI score of gastric signet ring cell carcinoma was significantly higher than that of gastric squamous cell carcinoma. The Pearson correlation analysis showed that the CRF BFI score was positively correlated with mood (r=0.423, P=0.008). There were significant differences in body function and mood (F=-16.254, F=-13.256, both P<0.05)and fatigue,pain and loss of appetite among 3 CRF groups(F=12.075,F=14.361,F=13.837, all P<0.05). There was a significant difference in the mean CRF BFI score between the three groups before and after chemotherapy(tSD=6.981,tPR=6.903,tPD=7.437,all P<0.05). Compared with pre-chemotherapy, the mean CRF BFI score of SD and PR group decreased after 3 months follow-up, score of PD group increased, the differences were statistically significant(t=2.371,t=6.912,t=18.237,all P<0.05).Conclusions The incidence of CRF in patients with advanced gastric cancer is very high,the degree of CRF has correlation with age, PS score and pathological type. Relieve symptoms such as fatigue, pain and loss of appetite and control adverse reactions could help to reduce the degree of CRF.