The main purpose of this study is to investigate the interactions between Lin28 and Her2 in gastric cancer. Lin28 and Her2 expression were evaluated in surgically resected samples of 298 gastric cancer patients using immunohistochemical staining. The correlations between Lin28/Her2 expression and clinical variables were retrospectively analyzed. The mRNA level of LIN28 and HER2 was detected by reverse-transcriptase polymerase chain reaction. Among all gastric cancer patients, 33.9% (101/298) were determined as Her2-positive, and 43.0% (128/298) were defined as Lin28-positive. Lin28 was significantly associated with Her2, advanced tumor stage, lesion size, and Ki67 level (p<0.05 for each). Kaplan-Meier analysis illustrated that both Lin28 and Her2 are poor prognostic factors in gastric cancer; Lin28(+)/Her2(+) patients have the poorest survival (median survival = 17 months, p<0.01). Multivariate Cox analysis showed that Lin28 is a significant prognostic factor (hazard ratio (HR) = 1.79, 95% confidence interval (CI) 1.23-2.62). Further stratification analysis indicated that Lin28 may be a prognostic factor in chemotherapy. In vitro data on MKN-28 and MKN-45 cells showed that Lin28 can upregulate Her2 expression at translational level. Both Lin28 and Her2 are poor prognostic factors in gastric cancer. Lin28 may regulate Her2 post-transcriptionally in gastric cancer cells, which indicates it might be a potential target in the treatment of gastric cancer.