Abstract Introduction: The most prevalent type of arthritis is osteoarthritis which is known with the degenerative knee disease. Limited pieces of evidence have indicated that satureja with special phenol compounds is effective in inflammation reduction and pain alleviation. The aim of this study was to investigate the effect of Satureja Hortensis powder supplement on pain improvement and serum TNF-α in patients with knee osteoarthritis(OA). Materials and Methods: The present study was conducted as a placebo-controlled double-blind randomized clinical trial. 39 patients with OA with medium pain were randomly divided into two groups which received Satureja Hortensis powder(SG) and placebo(PG) These groups consumed three 200 mg capsules with the same size and form for two months which contained Satureja Hortensis powder and starch, respectively. Pain intensity was determined using visual analogue scale(VAS) at the beginning and end of the trial. Response to the treatment was defined as pain reduction by more than 1.5 scores. The concentration of TNF-α were measured with ELISA kit. Results: To distribute pain intensity before the intervention, there was no significant difference between the two groups. Before the intervention, all people had a pain score between 4 and 7. After the intervention, 95% of the SG and 84% of the PG were in this scope. These changes were not statistically different(p=0.12). There was no significant difference between the two groups in concentration of TNF-α before and after the intervention. Conclusion: Results of this study showed that Satureja Hortensis powder supplement with dose of 600 mg per day for 60 days was not effective on pain alleviation and concentration of TNF-α in patients with knee osteoarthritis.