Assessing health-related quality of life (HRQOL) stands as a paramount outcome measure within medical research. Therefore, a specific questionnaire with sufficient levels of validity and reliability is among the most effective methods for assessing HRQOL. The scale development of Health-Related Quality of Life with Six Domains (HRQ-6D) was published in 2023. This scale measure health-related quality of life (HRQOL) within 24 h or today. It can be used to measure immediate patients’ outcome after clinical intervention or without intervention such as measuring patients’ outcome in an observational study. The HRQ-6D has 12 items constructed in six domains and three dimensions. The scale demonstrated excellent reliability and validity, along with a satisfactory model fit. Furthermore, it showed a significant association with real clinical evidence. This is the first review on the HRQ-6D to discuss the features and application of the HRQ-6D.