Indoor transmission of respiratory droplets bearing influenza within humans poses high risks to respiratory function deterioration and death. Therefore, we aimed to develop a framework for quantifying the influenza infection risk based on the relationships between inhaled/exhaled respiratory droplets and airborne transmission dynamics in a ventilated airspace. An experiment was conducted to measure the size distribution of influenza-containing droplets produced by coughing for a better understanding of potential influenza spread. Here we integrated influenza population transmission dynamics, a human respiratory tract model, and a control measure approach to examine the indoor environment–virus–host interactions. A probabilistic risk model was implemented to assess size-specific infection risk for potentially transmissible influenza droplets indoors. Our results found that there was a 50% probability of the basic reproduction number (R0) exceeding 1 for small-size influenza droplets of 0·3–0·4 µm, implicating a potentially high indoor infection risk to humans. However, a combination of public health interventions with enhanced ventilation could substantially contain indoor influenza infection. Moreover, the present dynamic simulation and control measure assessment provide insights into why indoor transmissible influenza droplet-induced infection is occurring not only in upper lung regions but also in the lower respiratory tract, not normally considered at infection risk.