Background: End-stage kidney disease (ESKD) patients undergoing hemodialysis suffer from multiple comorbidities, including cardiovascular disorders. Calcium phosphate product is one of the stand-alone cardiovascular risk markers. The relationship between calcium phosphate product-based cardiovascular risk and HRQOL needs to be further studied. Methods: This project was a cross-sectional survey using the Kidney Disease Quality of Life (KDQOL-36) of patient health-related quality of life (HRQOL). Calcium phosphate product was calculated from the information in the medical records. The study was conducted at the hemodialysis ward of the hospital affiliated with the Thumbay University. Spearman’s correlation coefficient (rs) was used to explore an association (correlation) between HRQOL domains and categorized calcium phosphate products. In this study, the significance level was set at P = 0.05, and SPSS software version 26 was used to analyze the data. Results: The mean score (58%) of the Short Form (SF)-12 Physical composite was lower than the mean score of mental composite (70%). Among kidney-specific domains, the highest HRQOL score was associated with the symptom/problem list (71%), followed by effects on kidney disease (63%) and the burden of kidney disease (40%), respectively. There was a non-strong negative correlation between the ‘burden of kidney disease’ and corrected calcium phosphate product (rs -0.439, P-value 0.032) and between ‘symptom/ problem list’ and corrected calcium phosphate product (rs -0.431, P-value 0.035), and the other KDQOL domains revealed insignificant relationship with calcium phosphate product. Conclusions: ESKD affects HRQOL in patients undergoing maintenance hemodialysis. Calcium phosphate product also needs to be decreased by < 55 mg/dL in the concerned patients. Calcium phosphate product and HRQOL were not correlated in this group of patients. The HRQOL measures need to be revised to detect cardiovascular risk.