The high prevalence of dialysis-related symptoms in maintenance hemodialysis (MHD) patients severely affect quality of life. Therefore, in this study, we assessed the dialysis symptom index (DSI) of MHD patients during the second wave of COVID-19, which triggered a health crisis, resulting in many cities in China opting for social isolation. A total of 106 MHD patients from our center were screened. DSI, sleep quality, and fatigue scales were investigated separately before and during lockdown. Demographic and laboratory data of MHD patients were collected. A nomogram was used to predict high DSI by combining multiple indicators. Additionally, internal validation was performed to reduce overfitting bias. The mean age of patients was 56.0 years (SD 13.1). The prevalence and severity of DSI were significantly higher during lockdown than pre-lockdown. Notably, itching, trouble staying asleep, bone or joint pain, muscle cramps, feeling irritability, difficulty concentrating, headache, constipation, and feeling nervous were observed ( P<0.05). Multivariate logistic regression analysis identified longer dialysis vintage, lower albumin level, and lower Kt/V as predictors of high DSI. Additionally, the nomogram showed good accuracy in estimating high DSI with a C-index and bootstrap-corrected index of 0.875 and 0.863, respectively. Moreover, calibration plots showed optimal consistency with the actual presence of high DSI. We found a higher prevalence of DSI in MHD patients during the COVID-19 lockdown. Furthermore, patients with longer dialysis vintage, lower albumin levels and Kt/V had a risk of developing high DSI. Further studies should identify targeted therapies for improving the symptom burden of MHD patients.