Objectives. This study aimed to observe the relationship among heavy metals concentration, microsatellite instability (MSI), and human epidermal growth factor receptor type 2 (HER2) gene amplification in gastric cancer (GC) patients. Methods. The concentrations of 18 heavy metals in the plasma of GC patients and healthy controls were measured by inductive coupled plasma emission spectrometry (ICP-MS). MSI detection was conducted by detecting 5 microsatellite repeat markers by PCR analysis. HER2 gene amplification was detected by fluorescence in situ hybridization (FISH). The relationship among heavy metal elements, tumor biomarkers, HER2 amplification, and MSI status was analyzed by Pearson correlation analysis. Results. A total of 105 GC patients and 62 healthy controls were recruited in this study. The concentration of arsenic (As), chromium (Cr), cuprum (Cu), mercury (Hg), manganese (Mn), lead (Pb), stibium (Sb), selenium (Se), stannum (Sn), strontium (Sr), thallium (Tl), vanadium (V), and zinc (Zn) were significantly different between GC patients and controls. Among 105 GC patients, including 87 microsatellite-stable (MSS) samples and 18 MSI samples, the concentration of Ga is significantly higher in the MSI group than that in the MSS group. Meanwhile, in 97 GC patients having detected HER2 gene amplification, 69 of 97 had negative HER2 gene amplification and the rest 28 GC patients had positive HER2 gene amplification. The concentration of Hg, Sn, and Tl is noticeably higher in the HER2 positive group than in the HER2 negative group. Only Sb was positively correlated with MSI, but none of these heavy metals was correlated with HER2 gene amplification. Conclusions. The results indicated that Sb has significant positive correlation with the MSI status, which suggests that Sb may cause MSI in GC. However, further research studies are required to elucidate the mechanisms in the near feature.