Aim To investigate the impact of policosanol combined with atorvastatin on high-density lipoprotein subfractions. Methods A total of 49 consecutively patients with hyperlipidemia were assigned to receive placebo (control group, n=17), atorvastatin 20 mg (n=16) or policosanol 20mg combined with atorvastatin 20 mg (n=16). The baseline clinical characteristics were collected and the HDL lipoprint system was used for lipid subfraction quantification. Results After 8 weeks’ treatment, the reduction of triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) was significant in both atorvastatin group and policosanol combined with atorvastatin group (P<0.05 or P<0.001, respectively), while the change of high-density lipoprotein cholesterol (HDLC) level had no significant difference (P>0.05). Both in groups of atorvastatin and policosanol combined with atorvastatin, large HDLC subfraction level and large HDLC subfraction percentage significantly increased after treatment (all for P<0.05), while small HDLC subfraction level and small HDLC subfraction percentage markedly reduced. Further analysis showed that the reduction of small HDLC subfraction level and small HDLC subfraction percentage was more marked (P<0.05 for atorvastatin group and P<0.001 for policosanol combined with atorvastatin, respectively) in policosanol combined with atorvastatin group compared to atorvastatin group. Conclusion After treatment with atorvastatin or policosanol combined with atorvastatin, the distribution of HDL subfractions was significantly improved by an increase of large HDL subfraction and a reduction of small HDL subfraction. The reduction of small HDLC subfraction level and percentage was more marked in policosanol combined with atorvastatin group than that in atorvastatin group.