The hemoglobin, albumin, lymphocyte, and platelet (HALP) values were marked as a original index of general nutritional and inflammatory conditions. The purpose of this investigation was to evaluate the potential relationship between HALP and prognosis in hemodialysis (HD) patients. Patients with maintenance HD from multiple dialysis centers in China were retrospectively analyzed. The primary poor outcome were cardiovascular disease (CVD) and all-cause death. The computational equation of HALP values as the follows: hemoglobin (g/L)×albumin (g/L)×lymphocytes (/L)/platelets (/L). All participants were divided into Tertile 1, Tertile 2, and Tertile 3 according to the tertiles of baseline HALP values. The Kaplan–Meier curve and the Cox regression was done to figure out the relationship about HALP and adverse outcomes. The restricted cubic splines further identified the possible associations. The time-dependent receiver operating characteristic curve and C-index were implemented for evaluate the predictive values of the HALP composite model. There were 4796 patients incorporate into ultimate study. Compared with patients in Tertile 1, patients in Tertile 3 had an lower risk of all-cause mortality [hazard ratios = 0.66, 95% confidence intervals: 0.49–0.86,P= .007] and CVD mortality [sub-distribution hazard ratio = 0.51, 95% confidence intervals: 0.34–0.80,P= .005]. The composite model with the supplement of HALP outperformed the traditional factor model in the time-dependent receiver operating characteristic curve. High HALP values at baseline are related to a diminished risk of CVD death and all-cause death in HD patients. HALP is a novel and potent index for the prognosis of HD patients.