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Liposarcoma (LPS) is one of the most common subtypes of sarcoma with a high recurrence rate. CENPF is a regulator of cell cycle, differential expression of which has been shown to be related with various cancers. However, the prognostic value of <i>CENPF</i> in LPS has not been deciphered yet. Using data from TCGA and GEO datasets, the expression difference of CENPF and its effects on the prognosis or immune infiltration of LPS patients were analyzed. As results show, <i>CENPF</i> was significantly upregulated in LPS compared to normal tissues. Survival curves illustrated that high <i>CENPF</i> expression was significantly associated with adverse prognosis. Univariate and multivariate analysis suggested that <i>CENPF</i> expression could be an independent risk factor for LPS. <i>CENPF</i> was closely related to chromosome segregation, microtubule binding and cell cycle. Immune infiltration analysis elucidated a negative correlation between <i>CENPF</i> expression and immune score. In conclusion, <i>CENPF</i> not only could be considered as a potential prognostic biomarker but also a potential malignant indicator of immune infiltration-related survival for LPS. The elevated expression of <i>CENPF</i> reveals an unfavorable prognostic outcome and worse immune score. Thus, therapeutically targeting CENPF combined with immunotherapy might be an attractive strategy for the treatment of LPS.