Treatment adherence (TA) is a critical issue and is under-investigated in hemodialysis patients. A multi-center study was conducted from July 2020 to March 2021 on 972 hemodialysis patients in eight hospitals in Vietnam to explore the factors associated with TA during the COVID-19 pandemic. Data were collected, including socio-demographics, an End-Stage Renal Disease Adherence Questionnaire (ESRD-AQ), 12-item short-form health literacy questionnaire (HLS-SF12), 4-item digital healthy diet literacy scale (DDL), 10-item hemodialysis dietary knowledge scale (HDK), 7-item fear of COVID-19 scale (FCoV-19S), and suspected COVID-19 symptoms (S-COVID19-S). Bivariate and multivariate linear regression models were used to explore the associations. Higher DDL scores were associated with higher TA scores (regression coefficient, B, 1.35; 95% confidence interval, 95%CI, 0.59, 2.12;p= 0.001). Higher FCoV-19S scores were associated with lower TA scores (B, −1.78; 95%CI, −3.33, −0.24;p= 0.023). In addition, patients aged 60–85 (B, 24.85; 95%CI, 6.61, 43.11;p= 0.008) with “very or fairly easy” medication payment ability (B, 27.92; 95%CI, 5.89, 44.95;p= 0.013) had higher TA scores. Patients who underwent hemodialysis for ≥5 years had a lower TA score than those who received <5 years of hemodialysis (B, −52.87; 95%CI, −70.46, −35.28;p< 0.001). These findings suggested that DDL and FCoV-19S, among other factors, should be considered in future interventions to improve TA in hemodialysis patients.