Exposure to UV radiation damages the skin and increases the risk of skin cancer. Sunscreen is used to protect the skin from the harmful effects of UV radiation. However, the chemical UV filters used in sunscreen can show toxicity and cause allergic reactions. A safe sunscreen that includes a lower content of chemical UV filters and exerts an excellent effect on UV protection needs to be developed. The objective of this study was to investigate whether the addition of afzelin to sunscreen could improve the sun protection factor (SPF). A synergistic effect between afzelin and organic sunscreen agents including padimate O and oxybenzone was confirmed. Interestingly, 100% in vitro SPF-boosting was observed when afzelin (0.05%) was applied with a standard SPF formulation containing organic sunscreens while afzelin alone had no contribution to the SPF. In vivo SPF analysis of the standard SPF formulation showed an SPF value of 13.3 that increased to 20.1 when supplemented with afzelin (0.05%). Additionally, afzelin showed no skin irritation in a human trial. These results suggest that afzelin is useful as a natural additive in sunscreen formulations and provides an SPF-boosting effect. Afzelin supplementation to the formulation showed the potential to reduce the use of synthetic photoprotectors, which could minimize the risk of synthetic agent toxicity.