Pulsation of gas flow created in pulse combustion drying has been shown to increase the overall heat and mass transfer coefficients during the drying process, resulting in process intensification. Some studies reported that pulse combustion drying could produce particles that are much smaller, even down to nanoscale, than those produced with normal spray drying. It is still unclear when and why pulse combustion drying might produce so small particles. It was argued in previous studies that the droplets undergo breakup during the drying process, and the difference in balance between two pressures, namely osmotic pressure and Laplace pressure, is responsible for droplet fragmentation. A droplet will breakup when the osmotic pressure due to interaction of nanoparticles becomes greater than the Laplace pressure that keeps the droplet as a unit. In the more classical theory, breakup of a spherical droplet situated in a fluid flow is determined by whether the force exerted by the fluid flow on the droplet surface can overcome the surface tension force. In the current study, breakup of a nano-suspension droplet during pulse combustion drying is modelled. From the difference between Laplace pressure and osmotic pressure, a new variable named modified surface tension is introduced. The results of simulation show how the key parameters in pulse combustion drying as well as the colloidal droplet properties influence the droplet breakup. For easier colloidal droplet breakup, a large droplet, small nanoparticles, high surface charge, higher gas temperature, stronger gas oscillation, and relatively high frequency are favorable. It is shown that while droplet breakup can result from pulse combustion drying conditions, it cannot be the main mechanism that makes nanoparticle production possible.