Coronavirus Disease 2019 (COVID-19) has caused a pandemic globally since its outbreak in 2019. As an important port city with prosperous foreign trade, Shanghai has been under severe pressure to prevent the input of COVID-19. With this in mind, solid policies and measures have always been taken in Shanghai to control the input of COVID-19 strictly. In March 2022, the SARS-CoV-2 Omicron variant swept Shanghai, and then the home office order was rapidly carried out in most of the districts. This article focuses on quantifying the changes in concentrations of PM10 and PM2.5 in Shanghai after implementing the home office order and exploring the spatial-distribution characteristics and time trend of the impact of the home office order on airborne particulate matters (PMs) through an interrupted-time-series (ITS) analysis. This study found that PM10 and PM2.5 decreased by 31.40 μg/m3 (p = 0.028) and 10.33 μg/m3 (p = 0.276), respectively, with the fastest decrease speed in the first 10 days of the home office order. Meanwhile, the changes in PM concentrations in eastern areas such as Fengxian District and Chongming District are less than those in central and western areas of Shanghai. Therefore, it can be concluded that implementing the home office order for 10 days could effectively cut down PM concentrations, and the reduction values can be affected by spatial difference and time factor.