Objective: To study the effect of intramuscular calcitonin injection combined with intra-articular ozone injection on the expression of the IL family and MMPs family of knee osteoarthritis. Methods: A total of 128 patients with knee osteoarthritis who were treated in the hospital between January 2015 and January 2017 were collected and divided into control group and observation group by random number table, each with 64 cases. Control group received intra-articular ozone injection therapy, and observation group received intramascular calcitonin injection combined with intra-articular ozone injection therapy. The differences in serum levels of IL family members and MMPs family members were compared between the two groups before and after treatment. Results:Before treatment, the differences in serum levels of IL family members and MMPs family members were not statistically significant between the two groups (P＞0.05). 1 week after treatment, serum levels of IL family members IL-1β, IL-15, IL-17 and IL-18 as well as MMPs family members MMP-1, MMP-2, MMP-3 and MMP-13 of both groups of patients were significantly lower than those before treatment (P<0.05), and serum IL-1β, IL-15, IL-17, IL-18, MMP-1, MMP-2, MMP-3 and MMP-13 levels of observation group were significantly lower than those of control group (P<0.05). Conclusion: Intramuscular calcitonin injection combined with intra-articular ozone injection therapy can effectively inhibit the expression of IL family and MMPs family in patients with knee osteoarthritis.