In endoscopic submucosal dissection (ESD), the narrow gastrointestinal space can cause difficulty in surgical interventions. Tissue ablation apparatuses with high-power CO₂ lasers or Nd:YAG lasers have been developed to facilitate endoscopic surgical procedures. We studied the interaction of 808-nm laser light with a porcine stomach tissue, with the aim of developing a therapeutic medical device that can remove lesions at the gastrointestinal wall by irradiating a near-infrared laser light incorporated in an endoscopic system. The perforation depths at the porcine fillet and the stomach tissues linearly increased in the range of 2–8mm in proportion to the laser energy density of 63.7–382 kJ/cm². Despite the distinct structural and compositional difference, the variation of the perforation depth between the stomach and the fillet was not found at 808-nm wavelength in our measurement. We further studied the laser–tissue interaction by changing the concentration of the methyl blue solution used conventionally as a submucosal fluidic cushion (SFC) in ESD procedures. The temperature of the mucosal layer increased more rapidly at higher concentration of the methyl blue solution, because of enhanced light absorption at the SFC layer. The insertion of the SFC would protect the muscle layer from thermal damage. We confirmed that more effective laser treatment should be enabled by tuning the opto-thermal properties of the SFC. This study can contribute to the optimization of the driving parameters for laser incision techniques as an alternative to conventional surgical interventions.