Gastric cancer (GC) is one of the most common malignancies in China, and chemotherapy is an important treatment for GC. However, drug resistance remains the main barrier to successful chemotherapy. Drug resistance is a complex phenomenon resulting from a combination of factors and mechanisms. The number of known relevant genes implicated in this phenomenon is growing rapidly. This review focuses on the mechanisms involved in the occurrence of drug resistance and explores the functions of several relevant genes in GC chemotherapy resistance.