For pre-operative osteoarthritis (OA) patients with varus knee, previous studies showed inconsistent results. Therefore, we conducted this study to better identify the association of Hospital for Special Surgery (HSS) score and mechanical alignment. 44 patients (51 knees) with constitutional varus knee caused by combined deformities (LDFA (lateral distal femoral angle) > 90°and MPTA (medial proximal tibial angle) < 85°)) were selected and analyzed with a mean follow-up period of 14 months after total knee arthroplasty (TKA). From January 2015 to December 2016, patients were collected consecutively after primary TKA. After filtering, fifty-one knees (44patients) were analyzed with a mean follow-up period of 14 months. All patients were divided into two groups based on post-operative hip-knee-ankle (HKA) acute angle: varus mechanical alignment (VMA) group (HKA < - 3°) and neutral mechanical axis (NMA) group (- 3° ≤ HKA ≤ 3°). 30 knees were included in the NMA group, and 21 knees in the VMA group. Comparisons of HSS between NMA group and VMA group were performed. After adjusting for age and Body Mass Index (BMI) confounders, Compared with NMA group, the HSS score in VMA group decreased by 0.81 units (95% CI, - 3.37 to 1.75) p = 0.5370). For pre-operative constitutional varus knee caused by combined deformities in chinese populations, no significant association between post-operative lower limb mechanical alignment and HSS score was found.