Low-grade myofibroblastic sarcoma (LGMS) is a rare, poorly differentiated, malignant tumor. The disease mainly occurs in the head and neck and rarely metastasizes at any age. Currently, there is no consensus regarding the treatment of metastatic LGMS. Here, we report the case of a 45-year-old man who was admitted to our hospital with cough for two weeks and abdominal pain for one week. Preoperative computed tomography revealed a large mass (116×35 mm) in both the lungs and jejunal mass (maximum diameter, 32 mm). The tumor was excised, and immunohistochemical staining was positive for SMA and CD117 and negative for desmin and CD34, indicating a case of LGMS. The patient was effectively treated with apatinib (250 mg/day) after failure of imatinib, liposomal doxorubicin, and ifosfamide. The progression-free survival time was 8.5 months, and the overall survival time was 17 months after treatment with apatinib. No grade 3 or 4 side effects were observed, except hand-foot syndrome. Whole-exome sequencing (WES) and RNA sequencing (RNA-seq) were performed on the patient's jejunal tumor and para-cancerous tissue samples, and bioinformatics analysis was performed on the results. WES identified five mutations in MKI67, OR2J2, EPPK1, FCGBP, and OR10G4. RNA-seq revealed that 1422 genes were upregulated and 1890 genes were downregulated. The differentially expressed genes were mainly enriched in the phosphatidylinositol 3-kinase (PI3K) signaling pathway, neuroactive ligand-receptor interaction signaling pathway, and cAMP signaling pathway. Our study indicated that apatinib may be a potential novel and effective treatment for LGMS.