We examined factors associated with healthcare cost, health-related quality of life (HRQOL), and kidney disease quality of life (KDQOL) in hemodialysis patients. We conducted a cross-sectional study on 160 patients from January to April 2019 at a hemodialysis center. Socio-demographic, clinical, and laboratory parameters and quality of life (QOL) (using KDQOL-SF-v1.3) were assessed. Monthly healthcare costs were extracted from the hospital information system. The means of healthcare cost, HRQOL, and KDQOL were VND 9.4 ± 1.6 million, VND 45.1 ± 21.9 and VND 51.3 ± 13.0, respectively. In the multivariate analysis, the healthcare cost was higher in patients with a longer hemodialysis vintage (regression coefficient (B): 0.74; 95% confidence interval (95% CI): 0.25; 1.23), comorbidity (B: 0.77; 95% CI: 0.24; 1.31); and lower in those with a higher hematocrit concentration (B: −0.07; 95% CI: −0.13; −0.01). Patients that lived in urban areas (B: 9.08; 95% CI: 2.30; 15.85) had a better HRQOL; those with a comorbidity (B: −14.20; 95% CI: −21.43; −6.97), and with hypoalbuminemia (B: −9.31; 95% CI: −16.58; −2.04) had a poorer HRQOL. Patients with a higher level of education (B: 5.38~6.29) had a better KDQOL; those with a comorbidity had a poorer KDQOL (B: −6.17; 95% CI: −10.49; −1.85). In conclusion, a longer hemodialysis vintage, a comorbidity and a lower hematocrit concentration were associated with higher healthcare costs. Patients who lived in urban areas had a better HRQOL and a higher level of education led to a better KDQOL. Patients with a comorbidity had a lower HRQOL and KDQOL. Malnourished patients had a lower HRQOL.