Osteoporosis and degenerative spinal disease are still an unsolvable surgical problem. It is still difficult to solve the complications related to postoperative osteoporosis, such as cage subsidence, displacement, and retraction. Expandable interbody cage is a recent innovation and an increasingly popular alternative to standard static cage. However, the clinical efficacy of MIS-TLIF combined with expandable cage for the treatment of osteoporosis has limited reports. The purpose of this paper was to analyze the efficacy of MIS-TLIF with expandable cage in patients with degenerative lumbar disease with osteoporosis. Patients with osteoporosis who received single-level MIS-TLIF and were followed up for at least 1 year were included. The outcome measures are as follows: clinical features, perioperative period, and neurological complications. JOA score and VAS pain score were used to analyze the improvement of patients’ function. Imaging analysis included segmental lordosis (SL), lumbar lordosis (LL), intervertebral disc height (DH), and the ratio of cage height to preoperative DH (RCD). The final data analysis included 284 patients with osteoporosis. 178 patients used static cages, and 106 patients used expandable cages. There was no significant difference in baseline characteristics, surgical indexes, and JOA and VAS scores between the two groups. There was no difference in SL or LL between static group and expandable group. There was no significant difference in preoperative DH between the two groups. The RCD in the expansion group was significantly lower than that in the static group. The intraoperative and postoperative sedimentation rate in the static group was significantly higher than that in the expandable group. The use of expandable cages in MIS-TLIF has shown good results for the treatment of degenerative lumbar diseases with osteoporosis. Through appropriate surgical techniques, the expandable cage can reduce the risk of cage sinking.