Objective This study aimed to investigate the influences of long noncoding RNA small nucleolar RNA host gene (SNHG) 22 on the proliferation, invasion, and migration of oral squamous cell carcinoma (OSCC) cells by regulating microRNA (miR)-27b-3p. Methods Cancer tissue and paracancerous tissue specimens of 52 OSCC patients were collected. Human normal oral keratinocytes (HOK) and three kinds of human OSCC cells (CAL-27, SCC-25, and HSC-3) were cultured in vitro. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of SNHG22 and miR-27b-3p in cancer tissues, adjacent tissues, HOK cells, and three kinds of OSCC cells. SCC-25 cells were transfected and separated into the following groups: control (no transfection), si-SNHG22, si-NC, miR-27b-3p inhibitor, inhibitor-NC, si-SNHG22+inhibitor-NC, and si-SNHG22+miR-27b-3p inhibitor. The proliferation of SCC-25 cells in each group was detected by cell-counting kit 8 method, and proliferation index (PI) was detected by flow cytometry. Transwell assay was applied to detect the invasion of SCC-25 cells in each group. Scratch-area healing experiment was applied to detect the migration of SCC-25 cells in each group. Dual-luciferase experiment was applied to verify the targeting relationship between SNHG22 and miR-27b-3p. Results Compared with adjacent tissues, SNHG22 expression in OSCC cancer tissues significantly increased, and the expression of miR-27b-3p significantly decreased (P<0.05). Compared with HOK cells, SNHG22 expression significantly increased in CAL-27 cells, SCC-25 cells, and HSC-3 cells, and the expression of miR-27b-3p significantly decreased. The expression in SCC-25 cells differed the most from that in HOK cells (P<0.05). Compared with the control group, the SCC-25 cell-proliferation rate, PI, invasion number, and scratch-area healing rate in the si-SNHG22 group decreased significantly (P<0.05). The SCC-25 cell-proliferation rate, PI, invasion number, and scratch-area healing rate in the miR-27b-3p inhibitor group increased significantly (P<0.05); compared with the si-SNHG22 group. The SCC-25 cell-proliferation rate, PI, invasion number, and scratch-area healing rate in the si-SNHG22+miR-27b-3p inhibitor group increased significantly (P<0.05). Dual-luciferase experiments showed that SNHG22 had a targeting relationship with miR-27b-3p. Conclusion SNHG22 was highly expressed in OSSC, whereas miR-27b-3p was lowly expressed. SNHG22 may promote the proliferation, invasion, and migration of SCC-25 cells through sponge miR-27b-3p. The SNHG22/miR-27b-3p axis may be a new diagnostic and therapeutic target for OSCC.