This study was to assess the expression of MACC-1 and c-MET in gastric cancer, and to correlate this expression with clinicohistological parameters and patient prognosis. Total RNA was extracted from cancer tissue and adjacent normal mucosa from frozen biopsy specimens of 30 patients with gastric cancer, and MACC-1 expression was assessed by RT-PCR. MACC-1 and c-MET protein expression were also assessed in paraffin-embedded tissues obtained from 436 tumor mucosa and 92 normal mucosa specimens by immunohistochemistry. The correlation between MACC-1 and c-MET expression and clinicopathological factors (age, sex, histology, tumor depth, lymph node status and vessel invasion) were also evaluated. RT-PCR analysis revealed that MACC-1 expression was significantly higher in cancerous mucosa compared with normal tissue. Immunohistochemical analysis indicated that MACC-1 and c-MET were moderately or strongly expressed in gastric cancer tissue, whereas expression was weak or absent in non-cancer tissue. Expression of MACC-1 or c-MET was significantly associated with larger tumor size, deeper tumor invasion, presence of lymph node metastasis, lymphatic involvement, venous invasion, distant metastasis and advanced clinical stage. However, only MACC-1 exhibited significantly greater expression in carcinomas from the higher age group. The intensity of MACC-1 and c-MET expression was also positively correlated. Survival analysis of the 436 gastric cancer patients revealed that patients in clinical stages I, II and III exhibiting lower MACC-1 and c-MET expression had a higher 5-year survival rate compared with patients expressing high levels of these proteins. Multivariate analysis revealed that MACC-1 and c-MET may be independent prognostic indexes of gastric carcinoma (P < 0.01). Our findings confirm that MACC-1 and c-MET expression is strongly related to gastric cancer stage and degree of malignancy, and is inversely correlated to patient prognosis. Thus, MACC-1 and c-MET may interact to promote tumorigenesis and their expression may be used as independent prognostic markers in gastric cancer.