To observe the effects of moxibustion with different frequency on the disease activity and fatigue of rheumatoid arthritis (RA) with liver and kidney deficiency on the basis of western medication treatment. A total of 135 RA patients with liver and kidney deficiency were randomly divided into a high-frequency moxibustion group (45 cases, 3 cases dropped out), a low-frequency moxibustion group (45 cases, 2 cases dropped out) and a western medication group (45 cases, 2 cases dropped out, 1 case discontinued). Leflunomide tablet was taken orally in the western medication group, once a day, 20 mg a time. On the basis of the treatment in the western medication group, moxibustion was applied at ashi points and bilateral Shenshu (BL 23) and Sanyinjiao (SP 6) in the two moxibustion groups, 15 min a time. The treatment was given once a day, 5 times a week in the high-frequency moxibustion group and once every other day, 3 times a week in the low-frequency moxibustion group. A total of 12-week treatment was required in the 3 groups. Before and after treatment, the 28 joint disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), TCM syndrome score, average grip strength (GS) of both hands, 30-second sit-to-stand (STS), timed up and go (TUG), 20-meter walk test (20MWT), self rating anxiety scale (SAS) score and self rating depression scale (SDS) score were observed; before treatment, after treatment and in follow-up of 1, 3 months after treatment completion, the scores of fatigue visual analogue scale (VAS), Bristol rheumatoid arthritis fatigue numerical rating scale (BRAF-NRS) and Bristol rheumatoid arthritis fatigue multi-dimensional questionnaire (BRAF-MDQ) were observed, and the relieving of disease was evaluated by American College of Rheumatology (ACR)20/50/70 standards in the 3 groups. After treatment, the DAS28 scores, ESR, CRP, RF, TCM syndrome scores, TUG, 20MWT, SAS scores and SDS scores were decreased compared with those before treatment (P<0.01, P<0.05), while the average GS of both hands and STS were increased compared with those before treatment (P<0.01, P<0.05) in the 3 groups. After treatment, in the high-frequency moxibustion group, the DAS28 score, ESR, CRP, TCM syndrome score, SAS score and SDS score were lower (P<0.01, P<0.05), while the average GS of both hands and STS were higher (P<0.01, P<0.05) than those in the low-frequency moxibustion group and the western medication group; the TUG and 20MWT were decreased compared with those in the western medication group (P<0.01, P<0.05). After treatment, in the low-frequency moxibustion group, the DAS28 score, ESR, CRP, TCM syndrome score, TUG, SAS score and SDS score were lower (P<0.05, P<0.01), while the average GS of both hands was higher (P<0.01) than those in the western medication group. In each time point after treatment, the scores of fatigue VAS and BRAF-NRS were decreased compared with those before treatment in the 3 groups (P<0.01), while the BRAF-MDQ scores were decreased compared with those before treatment in the high-frequency moxibustion group and the low-frequency moxibustion group (P<0.01). After treatment, the BRAF-MDQ score was decreased compared with that before treatment in the western medication group (P<0.01). In the high-frequency moxibustion group, the scores of fatigue VAS, BRAF-NRS and BRAF-MDQ of each time point after treatment were lower than those in the western medication group (P<0.01), the scores of fatigue VAS and BRAF-NRS in follow-up of 1 month after treatment completion as well as the BRAF-MDQ score after treatment were lower than those in the low-frequency moxibustion group (P<0.01, P<0.05). In the low-frequency moxibustion group, the scores of fatigue VAS, BRAF-NRS and BRAF-MDQ of each time point after treatment were lower than those in the western medication group (P<0.01, P<0.05). After treatment, the proportions of ACR20 and ACR50 in the high-frequency moxibustion group and the low-frequency moxibustion group were higher than those in the western medication group (P<0.01), the proportion of ACR70 in the high-frequency moxibustion group was higher than those in the low-frequency moxibustion group and the western medication group (P<0.05, P<0.01), and the proportion of ACR70 in the low-frequency moxibustion group was higher than that in the western medication group (P<0.05). On the basis of the western medication treatment, moxibustion can effectively reduce the disease activity and improve fatigue status in RA patients with liver and kidney deficiency, and its efficacy is positively correlated with treatment frequency.