Coronavirus disease 2019 (COVID-19) with the infection of SARS-CoV-2 has become a serious pandemic worldwide. However, only few studies focused on risk factors of prolonged SARS-CoV-2 RNA detection among patients with COVID-19. We included 206 adult patients with laboratory-confirmed COVID-19 from two hospitals between 23 Jan and 1 April 2020. Least absolute shrinkage and selection operator (LASSO) analysis was used to screen out independent risk factors of SARS-CoV-2 RNA detection. By multivariate binomial logistic regression analysis and Cox regression analysis, we further determined the associations between SARS-CoV-2 RNA detection and potential risk factors. All patients had two negative SARS-CoV-2 tests with 33 days of median duration of SARS-CoV-2 RNA detection (interquartile range: 25.2–39 days). LASSO and binomial logistic regression analyses suggested that delayed hospital admission (adjusted OR = 3.70, 95% CI: 1.82–7.50), hypokalemia, and subpleural lesion (adjusted OR = 4.32, 95% CI: 1.10–16.97) were associated with prolonged SARS-CoV-2 RNA detection. By LASSO and multivariate Cox regression analyses, we observed that delayed hospital admission, subpleural lesion, and high-dose corticosteroid use were independent risk factors of prolonged SARS-CoV-2 RNA detection. Early hospital admission shortened 5.73 days of mean duration of SARS-CoV-2 RNA detection than delayed hospital admission after adjusting confounding factors. Our study demonstrated that delayed hospital admission and subpleural lesion were associated with prolonged SARS-CoV-2 RNA detection among patients with COVID-19. The use of high-dose corticosteroids should be interpreted with extreme caution in treating COVID-19.