<p>The diffusion of particulate matter in street canyons is related to pedestrian health. There are many factors that affect the diffusion of particulate matter. However, previous studies usually focused on one single factor or two factors. A factor evaluation model of PM2.5 diffusion was established using a combination of orthogonal experiment design method and computational fluid dynamics technology in street canyons in Dalian. The sensitivity of factors to PM2.5 concentration in pedestrian area was studied, and a significant factor was analyzed in detail. The simulation results were consistent with the field measurement results. The results showed that the coefficient of determination (<i>R</i>²) and root mean square error (RMSE) of PM2.5 were 0.907 and 0.89 µg/m³, respectively. The <i>R</i>² and RMSE of temperature were 0.909 and 3.145 °C, respectively. Among the different factors studied, the lane number and vehicle arrangement mode were relatively more significant regarding the diffusion of particulate matter. The traffic flow pattern had the least effect. In addition, an enumeration experiment method was used to study the effect of the number of lanes on the diffusion of particulate matter in the pedestrian area in Dalian. It was recommended that 6 lanes be chosen in the urban planning of street canyon roads with serious pollution and high traffic flow to protect the health of pedestrians and to meet the needs of traffic volume. This study quantified the effects of seven factors and proposed an accurate prediction model for pedestrian area, providing guidance for analyzing the factors of pollutant diffusion in street canyons to reduce pedestrian exposure risk and urban planning to a certain extent.</p>