The bio-inertness and inferior osseointegration of polyetheretherketone (PEEK) affect its long-term lifetime in clinical applications, and appropriate surface modification is an effective way to enhance osseointegration of PEEK implants. In the present study, a strategy of combining sulfonation with alkali treatment was proposed to endow PEEK with rapid apatite deposition and thus enhanced bioactivity. After 3 min of sulfonation with 98% H2SO4, the sample (PEEK-S-3) showed an optimized surface microporous network and obviously improved hydrophilicity. Its contact angle reduced from the original 106 ± 2.3° to 88 ± 4.0°. After a further 24 h of NaOH treatment on PEEK-S-3, Na element was introduced into the obtained sample (PEEK-Na-24), which had a similar surface morphology and chemical structure with PEEK-S-3 and had a further reduced contact angle (77.9 ± 2.9°). The in vitro bioactivity tests showed that after only 3 days of immersion in simulated body fluid (SBF), PEEK-Na-24 was fully covered with a layer of uniform bone-like apatite. The apatite deposition sharply decreased the contact angle of the sample (PEEK-HA) to 16.6 ± 2.6° and increased its surface roughness to 1.05 ± 0.27 μm, leading to the enhanced adsorption of serum proteins on PEEK-HA. The in vitro cell culture indicated that all the three surface-modified samples (PEEK-S-3, PEEK-Na-24 and PEEK-HA) could promote the adhesion, spreading, proliferation and osteoblastic differentiation of MC3T3-E1 pre-osteoblasts, and PEEK-HA presented the best effect. Thus, the surface bioactive PEEK resulting from the optimized surface modification, i.e. combination of sulfonation, alkali treatment and biomimetic apatite deposition, could have good potential in clinical application.