Malignant psoas syndrome（MPS）is one of challenging cancer pain states, which is often refractory to conventional analgesic therapy. We report a case of a 67 years-old female patient suffering from left MPS caused by lumbar paravertebral malignant lymphoma. Tapentadol, a dual action analgesic, has relatively low affinity to mu-opioid receptor and provoke noradrenergic reuptake inhibition simultaneously. Neuropathic component is predominant in MPS. Tapentadol is reported to be a drug of choice for the treatment of neuropathic pain. Psoas compartment blockade is a choice of interventions to relieve severe thigh pain caused by a lesion of lumbar plexus which exists in a compartment between psoas and quadratus lumborum muscles. Pain and numbness in the affected left thigh region of the patient were well managed by opioid switching from oxycodone to tapentadol and supplemental psoas compartment blocks with a local anesthetic and dexamethasone. The activity of daily life and quality of life of the patient were dramatically improved. Tapentadol with psoas compartment blockade may be efficacious for the management of MPS.