Background Surgical impact may be associated with enhanced tumor growth and chemoresistance. This study aimed to evaluate the effect of surgical impact on the mRNA expression of survivin, epidermal growth factor receptor (EGFR), and human epidermal receptor (HER2) in tumors after pneumoperitoneum versus laparotomy. Methods Nude mice were inoculated intraperitoneally with human gastric cancer cells (MKN45). Then laparotomy, carbon dioxide (CO2) pneumoperitoneum, and anesthesia alone were performed randomly, after which EGFR, HER2, and survivin mRNA expression using reverse transcription-polymerase chain reaction (RT-PCR) was evaluated. Results The expression of EGFR and HER2 mRNA increased significantly after the experiment. However, it was higher after laparotomy than after CO2 pneumoperitoneum at almost all examined time points. Survivin mRNA expression increased significantly in the first 48 h, then returned to the control level. It was higher after laparotomythan after CO2 pneumoperitoneum 48 h after the surgical procedures. Conclusion The expression of EGFR, HER2, and survivin increased after each surgical procedure. However it was lower after CO2 pneumoperitoneum than after laparotomy. This might be associated with changes in the chemosensitivity of the remnant cancer cells after surgery, supporting the use of minimally invasive surgery for cancer.