White matter hyperintensities (WMH) are common in stroke. The influence of WMH on health-related quality of life (HRQoL) following a lacunar stroke is unknown. This study evaluated the impact of WMH on HRQoL in acute lacunar stroke. A cohort of 160 patients with acute lacunar stroke admitted to the stroke unit of a university-affiliated regional hospital in Hong Kong was recruited. Three months after the index stroke, a research assistant administered the Short Form-36 (SF-36) to assess HRQoL. The severity of WMH was evaluated with magnetic resonance imaging (MRI). In univariate analysis, the severity of deep WMH (DWMH) negatively correlated with patients' vitality (VT; p < 0.05), social function (SF; p < 0.001), role-emotional (RE; p < 0.01), mental health (MH; p < 0.01), and mental component summary (MCS; p < 0.001) scores of HRQoL. DWMH was independently associated with all of the above five SF-36 scores (p < 0.05) in linear regression analysis. These findings suggest that DWMH has a significant impact on the HRQoL of stroke survivors. The importance of DWMH in the long-term HRQoL in lacunar stroke warrants further investigation.