Aim To investigate whether sphingosine-1-phosphate (S1P) promotes LC3-associated phagocytosis via its receptor S1PR1, thereby enhancing the efferocytosis of THP-1-derived macrophages. Methods THP-1 monocytes were induced to differentiate into macrophages using 80 μg/L phorbol ester; 254 nm ultraviolet radiation was used to induce early apoptosis in Jurkat cells for cell phagocytosis experiments. Macrophages were treated with 0,0.5,1.0 and 1.5 μmol/L S1P for 12 h, or treated with 1.5 μmol/L S1P alone or in combination with S1PR1 antagonist W146, S1PR2 antagonist JTE-013, S1PR3 antagonist CAY10444 and ATG4B inhibitor NSC185058. Western blot was used to detect the expression levels of MerTK, Axl, Tyro3, LC3B and LAMP1, fluorescence-labeled apoptotic cells were applied in phagocytosis assays to evaluate phagocytic efficiency, ELISA was employed to measure the levels of pro-inflammatory factors (TNF-α, IL-6 and IL-1β) and anti-inflammatory factors (TGF-β, IL-4 and IL-10) in the supernatant. Results S1P could significantly enhance the phagocytic capacity of macrophages for apoptotic cells, and this effect was concentration-dependent. Specifically, the phagocytic efficiency of macrophages for apoptotic cells was significantly improved (P＜0.01); the expression of cell burial receptors MerTK, Axl and Tyro3 was markedly upregulated (P＜0.01); at the same time, levels of anti-inflammatory factors (TGF-β, IL-4 and IL-10) increased (P＜0.01), while pro-inflammatory factors (TNF-α, IL-6 and IL-1β) decreased (P＜0.01). The results of the S1P blockade experiment showed that blocking S1PR1 with W146 could reverse the efferocytosis of S1P (P＜0.05), while blocking S1PR2 or S1PR3 had no significant effect. S1P treatment significantly increased the gene and protein expression levels of LC3B and LAMP1 in macrophages (P＜0.01) and promoted lysosome maturation. After NSC185058 treatment, the phagocytic efficiency and anti-inflammatory factor secretion of macrophages decreased (P＜0.05). In addition, the inhibitory effect of blocking S1PR1 and LC3-related phagocytosis on efferocytosis was more significant (P＜0.01). Conclusion S1P significantly enhances the phagocytic clearance ability of THP-1-derived macrophages towards apoptotic cells through S1PR1-mediated LC3-related phagocytosis, and promotes the transformation of macrophages into anti-inflammatory phenotypes.